curcumin and Insulin-Resistance

The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities.

Topics: Adiponectin; Curcumin; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; PPAR gamma

Glycemic control is of utmost importance both as a preventive measure in individuals at risk of diabetes and in the management of patients with disturbed glycemia. Turmeric/curcumin has been extensively studied in this field. In the present systematic review and meta-analysis, we aimed at investigating the impact of turmeric/curcumin supplementation on glycemic control.. Major online databases (PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar) were systematically searched from inception up to October 2022. Relevant randomized controlled trials (RCTs) meeting our eligible criteria were included. Weighted mean differences (WMDs) with confidence intervals (CIs) were expressed using a random-effect model. Subgroup analyses were conducted to find the sources of heterogeneities. To detect risk of bias in the included studies, we used the Cochrane risk-of-bias tool. The registration number was CRD42022374874.. Out of 4182 articles retrieved from the initial search, 59 RCTs were included. Our findings suggested that turmeric/curcumin supplementation was significantly effective in improving fasting blood sugar (WMD: 4.60 mg/dl; 95% CI: 5.55, -3.66), fasting insulin levels (WMD: 0.87 μIU/ml; 95% CI: 1.46, -0.27), hemoglobin A1c (HbA1c) (WMD: 0.32%; 95% CI: 0.45, -0.19), and homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: 0.33; 95% CI: 0.43, -0.22).. Our results indicate that turmeric/curcumin supplementation can be considered as a complementary method in the management of disturbed glycemia.

Topics: Adult; Blood Glucose; Curcuma; Curcumin; Dietary Supplements; Glycemic Index; Humans; Insulin Resistance; Randomized Controlled Trials as Topic

Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD.. The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis.. The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from. Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

Topics: Alanine Transaminase; Anthocyanins; Aspartate Aminotransferases; Catechin; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Dietary Supplements; Genistein; Hesperidin; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Plant Extracts; Polyphenols; Resveratrol; Silymarin; Triglycerides

Polycystic ovary syndrome (PCOS) is a multi-factorial heterogeneous syndrome that has both adverse reproductive and metabolic implications for affected women and its management is a challenging clinical problem. Curcumin, as a phenolic compound with potent anti-inflammatory and antioxidant properties exerting positive effects on the lipid profile and insulin resistance, appears to be a valuable treatment regimen for patients with PCOS.. This study aimed to evaluate the efficacy and safety of curcumin in the treatment of PCOS.. Chinese databases (Chinese National Knowledge Infrastructure, China Biology Medicine Databases, VIP database, Wanfang Database, and Chinese Clinical Trial Registry) and English databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus and Clinical trials) were thoroughly investigated through screening randomized controlled trials on curcumin in PCOS published from the date of inception to May 2022. Standardized data search and abstraction were conducted following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Quantitative and qualitative analyses were performed. Heterogeneity was assessed using I. A total of 447 patients from seven randomized controlled trials were included in the meta-analysis. Results showed that the ingestion of curcumin decreased body mass index (WMD -0.267, 95% CI -0.450 to -0.084, P = 0.004, I. In light of presented findings, curcumin has beneficial effects on serum markers of inflammation, weight loss and glucose and lipid metabolism in patients with PCOS. The incidence of adverse reactions does not increase with the application of curcumin. However, a larger, more definitive study is needed to further investigate these results.. https://www.crd.york.ac.uk/prospero/, identifier CRD42022332394.

Topics: C-Reactive Protein; Curcumin; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome

The misuse and abuse of antibiotics in livestock and poultry seriously endanger both human health and the continuously healthy development of the livestock and poultry breeding industry. Plant-derived bioactive compounds (curcumin, capsaicin, quercetin, resveratrol, catechin, lignans, etc.) have been widely studied in recent years, due to their extensive pharmacological functions and biological activities, such as anti-inflammatory, antioxidant, antistress, antitumor, antiviral, lowering blood glucose and lipids, and improving insulin sensitivity. Numerous studies have demonstrated that plant-derived bioactive compounds are able to enhance the host's ability to resist or diminish diseases by regulating the abundance of its gut microbiota, achieving great potential as a substitute for antibiotics. Recent developments in both humans and animals have also highlighted the major contribution of gut microbiota to the host's nutrition, metabolism, immunity, and neurological functions. Changes in gut microbiota composition are closely related to the development of obesity and can lead to numerous metabolic diseases. Mounting evidence has also demonstrated that plant-derived bioactive compounds, especially curcumin, can improve intestinal barrier function by regulating intestinal flora. Furthermore, bioactive constituents can be also directly metabolized by intestinal flora and further produce bioactive metabolites by the interaction between the host and intestinal flora. This largely enhances the protective effect of bioactive compounds on the host intestinal and whole body health, indicating that the bidirectional regulation between bioactive compounds and intestinal flora has great application potential in maintaining the host's intestinal health and preventing or treating various diseases. This review mainly summarizes the latest research progress in the bioregulation between gut microbiota and plant-derived bioactive compounds, together with its application potential in humans and animals, so as to provide theoretical support for the application of plant-derived bioactive compounds as new feed additives and potential substitutes for antibiotics in the livestock and poultry breeding industry. Overall, based on this review, it can be concluded that plant-derived bioactive compounds, by modulating gut microbiota, hold great promise toward the healthy development of both humans and animal husbandry.

Topics: Animals; Curcumin; Gastrointestinal Microbiome; Humans; Insulin Resistance; Intestines; Obesity

Metabolic diseases are globally popular, and a systematic review and meta-analysis of turmeric and curcuminoids on glucose metabolism among people with metabolic diseases was performed.. We comprehensively searched Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, the Cochrane Library and two Chinese databases, Wanfang and CNKI for RCTs that focused on the effects of turmeric and curcuminoids on fasting blood glucose (FBG), hemoglobin A1C (HbA1c), fasting serum insulin (FSI) and HOMA-IR among patients with metabolic diseases. The FBG and HbA1c were the main outcomes to be analyzed. With random-effects models, separate meta-analyses were conducted by inverse-variance and reported as WMD with 95% CIs.. Evidence from 17 RCTs including 22 trials showed that turmeric and curcuminoids lowered FBG by - 7.86 mg/dL (95% CI: -12.04, -3.67 mg/dL; P = 0.0002), HbA1c by - 0.38% (95% CI: -0.52%, -0.23%; P < 0.00001) and HOMA-IR by - 1.01 (95% CI: -1.6, -0.42; P = 0.0008). Moreover, they decreased fasting serum insulin by - 1.69 mU/L (95% CI: -3.22, -0.16 mU/L; P = 0.03) after more than 8 weeks of intervention in a subgroup analysis.. Turmeric and curcuminiods decrease FBG, HbA1c and HOMA-IR significantly among subjects with metabolic disease. Additionally, they may have an effect on FSI concentrations if the intervention period is more than 8 weeks. However, attention should be paid to these outcomes due to the significant heterogeneity.

Topics: Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Diarylheptanoids; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Metabolic Diseases; Randomized Controlled Trials as Topic

Non-alcoholic fatty liver disease (NAFLD) is a disorder of excessive fat accumulation in the liver, known as steatosis, without alcohol overconsumption. NAFLD can either manifest as simple steatosis or steatohepatitis, known as non-alcoholic steatohepatitis (NASH), which is accompanied by inflammation and possibly fibrosis. Furthermore, NASH might progress to hepatocellular carcinoma. NAFLD and NASH prevalence is in a continuous state of growth, and by 2018, NAFLD became a devastating metabolic disease with a global pandemic prevalence. The pathophysiology of NAFLD and NASH is not fully elucidated, but is known to involve the complex interplay between different metabolic, environmental, and genetic factors. In addition, unhealthy dietary habits and pre-existing metabolic disturbances together with other risk factors predispose NAFLD development and progression from simple steatosis to steatohepatitis, and eventually to fibrosis. Despite their growing worldwide prevalence, to date, there is no FDA-approved treatment for NAFLD and NASH. Several off-label medications are used to target disease risk factors such as obesity and insulin resistance, and some medications are used for their hepatoprotective effects. Unfortunately, currently used medications are not sufficiently effective, and research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH. In this review article, we outline the different risk factors and pathophysiological mechanisms involved in NAFLD, diagnostic procedures, and currently used management techniques.

Topics: Curcumin; Humans; Insulin Resistance; Liver; Liver Transplantation; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Plant Preparations; Resveratrol; Risk Factors

The therapeutic effects of curcumin for polycystic ovary syndrome (PCOS) remain inconclusive. The present study aims to evaluate the effects of curcumin on glycemic control and lipid profile in patients with PCOS. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from the inception through 28 November 2020. Randomized control trials (RCTs), which enrolled adult patients with PCOS, compared curcumin with placebo regarding the glycemic control and lipid profile, and reported sufficient information for performing meta-analysis, were included. Three RCTs were included. Curcumin significantly improves fasting glucose (mean difference (MD): -2.77, 95% confidence interval (CI): -4.16 to -1.38), fasting insulin (MD: -1.33, 95% CI: -2.18 to -0.49), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (MD: -0.32, 95% CI: -0.52 to -0.12), and quantitative insulin sensitivity check index (QUICKI) (MD: 0.010, 95% CI: 0.003-0.018). It also significantly improves high-density lipoprotein (MD: 1.92, 95% CI: 0.33-3.51) and total cholesterol (MD: -12.45, 95% CI: -22.05 to -2.85). In contrast, there is no statistically significant difference in the improvement in low-density lipoprotein (MD: -6.02, 95% CI: -26.66 to 14.62) and triglyceride (MD: 8.22, 95% CI: -26.10 to 42.53) between curcumin and placebo. The results of the fasting glucose, fasting insulin, HOMA-IR, QUICKI, and total cholesterol are conclusive as indicated by the trial sequential analysis. Curcumin may improve glycemic control and lipid metabolism in patients with PCOS and metabolic abnormality without significant adverse effects. Further studies are advocated to investigate the potential effects of curcumin on hyperandrogenism.

Topics: Adult; Blood Glucose; Cholesterol; Curcumin; Dietary Supplements; Fasting; Female; Glycemic Control; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Triglycerides

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

Topics: Adipogenesis; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Curcumin; Diet; Dietary Supplements; Endoplasmic Reticulum; Fatty Acids, Unsaturated; Humans; Inflammation; Insulin Resistance; Intestines; Lipids; Macrophages; Obesity; Polyphenols; Resveratrol; Signal Transduction; Thermogenesis

Free fatty acids (FFAs) and fatty acid synthesis (FAS) activity have significantly contributed to disease states such as insulin resistance, obesity, type 2 diabetes, myocardial infarction, blood pressure, and several types of cancer. Currently, several treatment options are available for patients with these conditions. Due to safety concerns, adverse effects, limited efficacy, and low tolerability associated with many medications, the identification of novel agents with less toxicity and a more favorable outcome is warranted. Curcumin is a phenolic compound derived from the turmeric plant with various biological activities, including anticarcinogenic, antioxidant, antiinflammatory, and hypolipidemic properties. PubMed, Scopus, and Web of Science were searched up to February 2020 for studies that demonstrated the efficacy and mechanisms of curcumin action on FFAs, FAS, and β-oxidation activity, as well as the desaturation system. Most of the evidence is in-vivo and in-vitro studies that demonstrate that curcumin possesses regulatory properties on FFAs levels through its effects on FAS and β-oxidation activity as well as desaturation system, which could improve insulin resistance, obesity, and other FFAs-related disorders. The present study provides a review of the existing in-vitro, in-vivo, and clinical evidence on the effect of curcumin on FFAs and FAS activity, β-oxidation, and desaturation system.

Topics: Curcumin; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Humans; Insulin Resistance; Lipid Metabolism

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment strategies for T2DM and insulin resistance lack in efficacy resulting in the need for new approaches to prevent and manage/treat the disease better. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (I of II) summarizes the existing in vitro studies examining the antidiabetic effects of curcumin, while a second (II of II) review summarizes evidence from existing in vivo animal studies and clinical trials focusing on curcumin's antidiabetic properties.

Topics: Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance

Heme oxygenase (HO) is a critical component of the defense mechanism to a wide variety of cellular stressors. HO induction affords cellular protection through the breakdown of toxic heme into metabolites, helping preserve cellular integrity. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition by which the liver accumulates fat. The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic. NALFD can progress to nonalcoholic steatohepatitis (NASH), advancing further to liver cirrhosis or cancer. NAFLD is also a contributing factor to cardiovascular and metabolic diseases. There are currently no drugs to specifically treat NAFLD, with most treatments focused on lifestyle modifications. One emerging area for NAFLD treatment is the use of dietary supplements such as curcumin, pomegranate seed oil, milk thistle oil, cold-pressed

Topics: Animals; Bilirubin; Biological Products; Curcumin; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Insulin Resistance; Liver; Non-alcoholic Fatty Liver Disease; Oxidoreductases Acting on CH-CH Group Donors; Reactive Oxygen Species

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment approaches to insulin resistance and T2DM lack in efficacy, resulting in the need for new approaches to prevent and treat the disease. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects, including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (II of II) summarizes the existing in vivo studies examining the antidiabetic effects of curcumin.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Mice; Oxidative Stress; Rats

Recent controversy regarding the therapeutic potential of curcumin indicates the challenges to research in this field. Here, we highlight the investigations of curcumin and other plant-derived polyphenols that demonstrate their application to metabolic diseases, in particular, obesity and diabetes. Thus, a number of preclinical and clinical investigations have shown the beneficial effect of curcumin (and other dietary polyphenols) in attenuating body weight gain, improving insulin sensitivity, and preventing diabetes development in rodent models and prediabetic subjects. Other intervention studies with dietary polyphenols have also found improvements in insulin resistance. Recent studies suggest that the metabolic effects of curcumin/polyphenols are linked to changes in the gut microbiota. Thus, research into curcumin continues to provide novel insights into metabolic regulation that may ultimately translate into effective therapy.

Topics: Animals; Curcumin; Diabetes Mellitus; Diet; Energy Metabolism; Humans; Insulin Resistance; Obesity; Phytotherapy; Polyphenols; Signal Transduction

Numerous natural products available over the counter are commonly consumed by healthy, sub-healthy or ill people for the treatment and prevention of various chronic diseases. Among them, a few dietary polyphenols, including the curry compound curcumin, have been attracting the most attention from biomedical researchers and drug developers. Unlike many so-called "good drug candidates", curcumin and several other dietary polyphenols do not have a single known therapeutic target or defined receptor. In addition, the bioavailability of these polyphenols is usually very low due to their poor absorption in the gut. These recently debated features have created enormous difficulties for drug developers. In this review, I do not discuss how to develop curcumin, other dietary polyphenols or their derivatives into pharmaceutical agents. Instead, I comment on how curcumin and dietary polyphenol research has enriched our knowledge of insulin signaling, including the presentation of my perspectives on how these studies will add to our understanding of the famous hepatic insulin function paradox.

Topics: Animals; Anthocyanins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Line; Curcumin; Drug Discovery; Fibroblast Growth Factors; Humans; Insulin; Insulin Resistance; Nuclear Proteins; Polyphenols; Resveratrol; Signal Transduction; Stilbenes; Transcription Factors

Curcumin, the bioactive component of turmeric, has been used for the treatment of several diseases including diabetes and its complications. Curcumin has been shown to exert pleiotropic effects by modulating different signaling molecules, including transcription factors, chemokines, cytokines, and adipokines. Disturbed regulation of adipokines, which include adiponectin, leptin, resistin, and visfatin, are implicated in the development of insulin resistance and Type 2 diabetes. Here, we review the findings of in vitro, in vivo, and clinical studies on the modulating effects that curcumin treatment exerts on adipokines. Additionally, we examine the potential beneficial effects of the activity of curcumin in the prevention and treatment of diabetes and its comorbidities. J. Cell. Biochem. 118: 4170-4182, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Adipokines; Animals; Curcumin; Cytokines; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Male

The objective of this systematic review was to assess available scientific data on the efficacy and safety of medicinal food plants for the treatment of impaired glucose tolerance.. We included randomized controlled trials (RCTs) with a minimum follow-up period of 6weeks. The diagnosis was determined by fasting plasma glucose values after two-hour oral glucose tolerance testing (OGTT). Two authors independently extracted data and evaluated bias. The Cochrane tool of risk of Bias Tool was used.. This review included ten trials. Most studies were highly biased as data were incomplete or reporting was selective. The two-hour fasting plasma glucose after the curcumin extract intervention showed statistical significance after 3, 6 and 9months: p<0.01. Also, glycosylated haemoglobin levels A1c (HbA1c) values after curcumin extract intervention showed statistical significance after 3, 6 and 9months: p<0.01. Insulin resistance (HOMA-IR) after curcumin extract intervention showed statistical significance after 6months and after 9months: p<0.05 and p<0.01.. Curcumin has shown the confident results to be effective for the treatment of impaired glucose tolerance. Fenugreek and flaxseed may also be effective, but due to low quality of these studies the results must be interpreted with caution.

Topics: Blood Glucose; Curcuma; Curcumin; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Phytotherapy; Plant Extracts; Plants, Medicinal; Randomized Controlled Trials as Topic

Metabolic Syndrome (MetS), affecting at least 30% of adults in the Western World, is characterized by three out of five variables, from high triglycerides, to elevated waist circumference and blood pressure. MetS is not characterized by elevated cholesterolemia, but is rather the consequence of a complex interaction of factors generally leading to increased insulin resistance. Drug treatments are of difficult handling, whereas well-characterized nutraceuticals may offer an effective alternative. Among these, functional foods, e.g. plant proteins, have been shown to improve insulin resistance and reduce triglyceride secretion. Pro- and pre-biotics, that are able to modify intestinal microbiome, reduce absorption of specific nutrients and improve the metabolic handling of energy-rich foods. Finally, specific nutraceuticals have proven to be of benefit, in particular, red-yeast rice, berberine, curcumin as well as vitamin D. All these can improve lipid handling by the liver as well as ameliorate insulin resistance. While lifestyle approaches, such as with the Mediterranean diet, may prove to be too complex for the single patient, better knowledge of selected nutraceuticals and more appropriate formulations leading to improved bioavailability will certainly widen the use of these agents, already in large use for the management of these very frequent patient groups. Key messages Functional foods, e.g. plant proteins, improve insulin resistance. Pro- and pre-biotics improve the metabolic handling of energy-rich foods. Nutraceutical can offer a significant help in handling MetS patients being part of lifestyle recommendations.

Topics: Berberine; Biological Products; Blood Glucose; Blood Pressure; Curcumin; Dietary Supplements; Female; Humans; Insulin Resistance; Lipoprotein Lipase; Male; Metabolic Syndrome; Plant Proteins, Dietary; Prebiotics; Probiotics; Risk Factors; Vitamin D; Waist Circumference

As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance. Cellular signaling research indicated that partial factors play significant roles in fructose-induced NAFLD, involving liver X receptor (LXR)α, sterol regulatory element binding protein (SREBP)-1/1c, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), peroxisome proliferator-activated receptor α (PPARα), leptin nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), c-Jun amino terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Until now, a series of natural products have been reported as regulators of NAFLD in vivo and in vitro. This paper reviews the natural products (e.g., curcumin, resveratrol, and (-)-epicatechin) and their mechanisms of ameliorating fructose-induced NAFLD over the past years. Although, as lead compounds, natural products usually have fewer activities compared with synthesized compounds, it will shed light on studies aiming to discover new drugs for NAFLD.

Topics: Animals; Biological Products; Catechin; Curcumin; Fructose; Humans; Inflammation; Insulin Resistance; Lipogenesis; Mitochondria; Non-alcoholic Fatty Liver Disease; Resveratrol; Stilbenes

Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016.

Topics: Animals; Antioxidants; Clinical Trials as Topic; Curcumin; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Molecular Targeted Therapy; Obesity; Oxidative Stress; Receptor, Insulin

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega-3-PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.

Topics: Adipokines; Animals; Carotenoids; Curcumin; Fatty Acids, Omega-3; Fatty Liver; Flavonols; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Polyphenols; Resveratrol; Stilbenes

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome.

Topics: Adipose Tissue; Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Delivery Systems; Humans; I-kappa B Proteins; Inflammation; Insulin; Insulin Resistance; Liver; Liver Diseases; Nanoparticles; NF-kappa B; NF-KappaB Inhibitor alpha; Obesity; Randomized Controlled Trials as Topic

Adipose tissue has an important endocrine function in the regulation of whole-body metabolism. Obesity leads to a chronic low-grade inflammation of the adipose tissue, which disrupts this endocrine function and results in metabolic derangements, such as type-2 diabetes. Dietary bioactive compounds, such as polyphenols and certain fatty acids, are known to suppress both systemic and adipose tissue inflammation and have the potential to improve these obesity-associated metabolic disorders. Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway in adipose tissue. Dietary polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), conjugated linoleic acid (CLA) and monounsaturated fatty acids (MUFA), such as oleic acid, also impart anti-inflammatory effects through several mechanisms. These include activation of AMPK and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as suppression of toll-like receptors (TLRs) and NF-κB pathway. This review discusses the major molecular mechanisms of dietary polyphenols and fatty acids, alone or in combination, which are responsible for adipose tissue-associated anti-inflammatory effects.

Topics: Adipose Tissue; Curcumin; Endocrine Glands; Fatty Acids; Food; Humans; Inflammation; Insulin Resistance; Polyphenols; Quercetin; Resveratrol; Stilbenes

Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Dietary Supplements; Humans; Inflammation; Insulin Resistance; Metabolic Syndrome; Obesity

Topics: Adult; Blood Glucose; Cholesterol; Curcuma; Double-Blind Method; Humans; Hypertension; Inflammation; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Abdominal

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to cartilage damage with mostly accompanied by metabolic disorders. This study aimed to investigate the effects of curcumin supplementation on metabolic parameters (lipid profile and glycemic indices), inflammatory factors, visfatin levels, and obesity values in women with RA. This randomized, double-blind, placebo-controlled clinical trial was conducted on 48 women with RA. The patients were treated with curcumin (500 mg once a day) or placebo for 8 weeks. Fasting blood samples, anthropometric measurements, dietary intakes, and physical activity levels of subjects were collected at baseline and the end of the study. Curcumin supplementation significantly decreased homeostatic model assessment for insulin resistance (HOMA-IR), erythrocyte sedimentation rate, serum levels of high-sensitivity C-reactive protein and triglycerides, weight, body mass index, and waist circumference of patients compared with the placebo at the end of the study (p < .05 for all). HOMA-IR and triglyceride levels significantly increased within the placebo group. Changes in fasting blood sugar, insulin, other lipids profile, and visfatin levels were not significant in any of the groups (p > .05). These results support the consumption of curcumin, as a part of an integrated approach to modulate metabolic factors, inflammation, and adiposity in women with RA.

Topics: Arthritis, Rheumatoid; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Male; Nicotinamide Phosphoribosyltransferase; Obesity

Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS).. We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS.. In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements.. Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial.. Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.

Topics: Adolescent; Adult; Androgens; Blood Glucose; Curcumin; Dehydroepiandrosterone; Dietary Supplements; Double-Blind Method; Female; Hirsutism; Humans; Hyperglycemia; Insulin; Insulin Resistance; Middle Aged; Placebos; Polycystic Ovary Syndrome; Treatment Outcome; Young Adult

Metabolic syndrome (MetS) is one of the most important health hazards. Curcumin is extracted from Curcuma longa (turmeric), which can affect the components of MetS. To increase the oral bioavailability of curcumin, nano-micelle curcumin is used instead of curcumin powder. In this randomized, double-blind, controlled clinical trial, 50 patients with MetS were randomly assigned to two groups to receive either 80 mg/day nano-curcumin (n = 25) or placebo (n = 25), for 12 weeks anthropometric measurements, blood pressure, and biochemical factors-including fasting blood sugar (FBS), Hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), pancreatic β cell function (HOMA-β) and lipid profile-were assessed at the baseline and the end of the study. Statistical analyses were done using SPSS software (Version 23). The analysis between the two groups has illustrated a significant reduction in the average change of triglyceride (TG) levels (-60.5 ± 121.7 vs. 13.1 ± 78.1 mg/dL; p < .05) and HOMA-β (-5.7 ± 48.2 vs. -4.01 ± 16.9; p < .05). But there were no significant differences in anthropometric measurements, blood pressure and biochemical factors-including FBS, HbA1c, HOMA-IR, HOMA-β, and lipid profile variables include (total cholesterol, LDL-C, and HDL-C) at the end of the study. In conclusion, supplementation with nano-micelle curcumin significantly improved serum TG in MetS patients.

Topics: Blood Glucose; Blood Pressure; Curcumin; Dietary Supplements; Double-Blind Method; Glycemic Control; Humans; Insulin Resistance; Lipids; Metabolic Syndrome; Nanomedicine

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically. It has been shown that curcumin also exhibits insulin-sensitizing properties. Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome. This clinical trial was conducted on 100 women with PCOS, diagnosed according to the Rotterdam criteria, who were sequentially recruited and randomly divided into two groups (n = 50 each). Group 1 received 500 mg metformin three times daily and group 2 received 80 mg/day capsule of curcumin nanomicelle and 500 mg metformin three times a day for 3 months. After collecting fasting blood samples, biochemical parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, plasma glucose, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were evaluated based on enzymatic methods. Hormonal parameters were assessed using immunoassay kits. Insulin resistance (HOMA-IR) and insulin-sensitivity check index (QUICKI) were also assessed. After treatment, fasting insulin, HOMA-IR, and total testosterone in group 2 were significantly lower than those in group 1 (p < 0.05). Post-treatment LDL-C levels in groups 1 and 2 were 117.9 ± 24 and 91.12 ± 19.46 mg/dL, respectively (p < 0.01). In addition, HDL-C levels were increased with curcumin (group 1: 38.1 ± 4.36 mg/dL; group 2: 44.12 ± 7.3 mg/dL, p < 0.05). Total cholesterol was decreased with curcumin level (group 1: 207.9 ± 39.84 mg/dL; group 2; 159.7 ± 48.43 mg/dL, p < 0.05), with a decrease in triglycerides levels (group 1: 141.6 ± 9.57; group 2: 97.5 ± 8.8 mg/dL, p < 0.01). This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS. Therefore, the combined use of metformin and curcumin may have therapeutic utility in patients with PCOS.

Topics: Blood Glucose; Curcumin; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Metformin; Polycystic Ovary Syndrome

Management of prediabetes is a critical step to prevent type-2 diabetes. Curcumin and zinc have been studied as an antioxidant, antiinflammatory, and antidiabetic agents. In this clinical trial, 84 subjects were randomized into curcumin (500 mg), zinc (30 mg), zinc and curcumin, and placebo groups for 90 days. At the baseline and the end of the study, the outcomes (fasting plasma glucose (FPG), 2-hour postprandial glucose (2hpp), HbA

Topics: Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Supplements; Double-Blind Method; Humans; Insulin; Insulin Resistance; Obesity; Overweight; Prediabetic State; Zinc

The aim of this study was to evaluate the effect of curcumin on body weight, glycemic control and serum lipids in women suffering from polycystic ovary syndrome (PCOS).. The current randomized, double-blinded, placebo-controlled clinical trial was performed on 60 subjects with PCOS, aged 18-40 years old. Subjects were randomly allocated to take 500 mg/day curcumin (n = 30) or placebo (n = 30) for 12 weeks. Glycemic control and serum lipids were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was evaluated.. Overall, curcumin administration for 12 weeks to women with PCOS had beneficial effects on body weight, glycemic control, serum lipids except triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ and LDLR. Registered under Clinical Trials.gov Identifier no. http://www.irct.ir: IRCT20170513033941N50.

Topics: Adolescent; Adult; Body Weight; Cholesterol; Curcumin; Double-Blind Method; Fasting; Female; Gene Expression; Glycemic Control; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Lipids; Polycystic Ovary Syndrome; Receptors, LDL; Triglycerides; Young Adult

Curcumin has shown to exert a positive impact on human glucose metabolism, even if its bioavailability is usually very low. The present study aimed to explore the effect of phosphatidylserine- and piperine-containing curcumin phytosomes on a large number of metabolic parameters related to insulin resistance, in the context of a randomized double-blind placebo-controlled trial involving 80 overweight subjects with suboptimal fasting plasma glucose.. Subjects were randomized to be treated with indistinguishable tablets (2 per day, to be taken after dinner) containing 800 mg phytosomal curcumin (Curserin®: 200 mg curcumin, 120 mg phosphatidylserine, 480 mg phosphatidylcholine and 8 mg piperine from Piper nigrum L. dry extract) for 8 weeks.. After 56-day treatment, the curcumin-treated group experienced a significant improvement in fasting plasma insulin (FPI), HOMA index, waist circumference, blood pressure, triglycerides (TG), HDL-C, liver transaminases, gamma-GT, index of liver steatosis and serum cortisol compared to the baseline. FPI, TG, liver transaminases, fatty liver index and serum cortisol level also significantly improved compared with the placebo-treated group. Compared to the baseline, at the end of the study placebo group experienced an improvement only in FPG and TG.. In conclusion, the present trial shows that supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose.

Topics: Curcumin; Double-Blind Method; Female; Humans; Hydrocortisone; Insulin; Insulin Resistance; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a major global health problem. The most common cause of death in these patients is due to cardiovascular disorders. The aim of this study was to examine the effects of curcumin supplementation on cardiovascular risk factors in patients with NAFLD.. In this randomized, placebo-controlled, clinical trial, fifty two patients with NAFLD were randomly assigned to receive life style recommendations plus either 1500 mg curcumin or placebo for 12 weeks. Anthropometric indices, blood lipid profile, insulin resistance, as well as hepatic steatosis and fibrosis scores were measured at the beginning and the end of the study, and compared between and within groups.. Hepatic fibrosis, serum cholesterol, glucose and alanin aminotransferase (ALT) reduced significantly only in curcumin group (p < 0.05). Anthropometric indices, blood lipid profile, insulin resistance, and hepatic steatosis decreased significantly in both groups (p < 0.05), without any significant difference between two groups.. Our results showed that daily intake of 1500 mg curcumin plus weight loss is not superior to weight loss alone in amelioration of cardiovascular risk factors in patients with NAFLD. Further studies with different dosages of curcumin are needed to be able to conclude about the effects of this dietary supplement on cardiovascular risk factors and NAFLD characteristics.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Homeostasis; Humans; Insulin Resistance; Iran; Lipids; Liver; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

Lowering insulin resistance and dyslipidaemia may not only enhance glycaemic control but also preserve the β-cell function, reducing the overall risk of developing type 2 diabetes (T2D). The current study was aimed to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) supplementation on glycaemic control and blood lipid levels in individuals at high risk of developing T2D.. This was a 2 × 2 factorial, randomised, double-blinded, placebo-controlled study. Participants were allocated to either double placebo (PL) or curcumin plus placebo matching for LCn-3PUFA (CC), or LCn-3PUFA plus placebo matching for curcumin (FO), or curcumin plus LCn-3PUFA (CC-FO) for twelve weeks. Primary outcome of the trial was glycaemic indices (HbA1C, fasting glucose and insulin). Insulin resistance and sensitivity is measured using homeostatic model assessment model.. A total of sixty-four participants (PL, n = 16; CC, n = 15; FO, n = 17, CC-FO, n = 16) were included in the final analysis. Post-intervention, HbA1c and fasting glucose remained unchanged across all the groups. Insulin sensitivity was significantly improved in the CC supplemented group (32.7 ± 10.3%) compared to PL (P = 0.009). FO and CC-FO tended to improve insulin sensitivity by 14.6 ± 8.5% and 8.8 ± 7.7% respectively, but the difference did not reach significance. Triglyceride levels were further increased in the PL (26.9 ± 7.4%), however, CC and CC-FO supplementation reduced the triglycerides, FO resulted in the greatest reduction in triglycerides (- 16.4 ± 4.5%, P < 0.001).. Reduction in insulin resistance and triglycerides by curcumin and LCn-3PUFA appears to be attractive strategies for lowering the risk of developing T2D. However, this study failed to demonstrate complimentary benefits of curcumin and LCn-3PUFA on glycaemic control.. ACTRN12615000559516 .

Topics: Adult; Aged; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Fasting; Fatty Acids, Omega-3; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Risk Factors; Triglycerides

Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin.. This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care.. 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎.. The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised.. A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study.. This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use.. IRCT2016071915536N3; pre-results.

Topics: Adult; Body Mass Index; Curcumin; Dietary Supplements; Exercise; Female; Humans; Insulin; Insulin Resistance; Iran; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Research Design

Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin. This study aimed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome.. In this pilot, randomized, double-blind, placebo-controlled trial, subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were randomly assigned to curcumin (n = 59; 1000 mg/d) or a placebo (n = 58) for 8 wk. Serum adiponectin and leptin concentrations were determined before and after intervention. The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using random-effects metaanalysis.. Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels (P < 0.001) and a reduction in serum leptin concentrations (P < 0.001). Serum leptin:adiponectin ratio was also improved by curcumin (P < 0.001). These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response. Metaanalysis suggested that curcumin supplementation can increase adiponectin levels by 76.78% (95% CI: 6.14-147.42; P = 0.0330), and reduce leptin by 26.49% (95% CI: -70.44 to 17.46), however this latter effect size did not reach statistical significance (P = 0.238).. Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome. This trial was registered at the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/) under Trial No. UMIN000018339.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Pilot Projects

Cognitive impairment develops with pre-diabetes and dementia is a complication of diabetes. Natural products like turmeric and cinnamon may ameliorate the underlying pathogenesis.. People ≥ 60 years (n=48) with newly-recognised untreated pre-diabetes were randomised to a double-blind metabolic study of placebo, turmeric (1 g), cinnamon (2 g) or both (1 g & 2 g respectively), ingested at a white bread (119 g) breakfast. Observations were made over 6 hours for pre- and post-working memory (WM), glycaemic and insulin responses and biomarkers of Alzheimer's disease (AD)(0, 2, 4 and 6 hours): amyloid precursor protein (APP), γ-secretase subunits presenilin-1 (PS1), presenilin-2 (PS2), and glycogen synthase kinase (GSK-3β). Differences between natural product users and non-users were determined by Students t and chi square tests; and between pre-test and post-test WM by Wilcoxon signed rank tests. Interaction between turmeric and cinnamon was tested by 2-way ANOVA. Multivariable linear regression (MLR) took account of BMI, glycaemia, insulin and AD biomarkers in the WM responses to turmeric and cinnamon.. No interaction between turmeric and cinnamon was detected. WM increased from 2.6 to 2.9 out of 3.0 (p=0.05) with turmeric, but was unchanged with cinnamon. WM improvement was inversely associated with insulin resistance (r=-0.418, p<0.01), but not with AD biomarkers. With MLR, the WM responses to turmeric were best predicted with an R2 of 34.5%; and with significant turmeric, BMI and insulin/glucose AUC beta-coefficients.. Co-ingestion of turmeric with white bread increases working memory independent of body fatness, glycaemia, insulin, or AD biomarkers.. 背景：認知功能失調伴隨糖尿病前期與失智症是糖尿病的併發症之ㄧ。天然食品如薑黃及 肉桂可改善此致病機轉。本研究為評估薑黃肉桂如何影響糖尿病前期患者認知功能之代謝 研究。方法：對象為三軍總醫院參加老人健檢者，納入條件為其空腹血糖介於100-126 mg/dL，共計48 位參與者。經由雙盲性別分層隨機分派至服用口服降血糖藥物或其組合、 薑黃、肉桂或其組合及控制組共4 組，每組12 名，男女各半。參與者須於報到後抽取空 腹血液、實施工作記憶前測及測量基本體位資料。再於8 時服用早餐及受試藥物，各組分 別為安慰劑、薑黃1 克、肉桂2 克、肉桂2 克與薑黃1 克等。隨後每隔2 小時採集血液， 共4 次，於最後1 次抽血完畢後，再測工作記憶分數。利用RT-PCR 技術測得APP、 PS1、PS2、GSK-3βmRNA 表現量。利用t 檢定及卡方檢定比較天然食品使用者及非使用 者平均值之差異；魏克森符號等級檢定工作記憶前測及後測的分數。利用雙因子變異數分 析檢定薑黃與肉桂兩植物成分之交互作用。複迴歸模式分析校正身體質量指數、血糖、胰 島素濃度、阿茲海默症相關之生物標記後，薑黃肉桂對工作記憶之影響。結果：薑黃與肉 桂兩植物成分並無交互作用產生。有服用薑黃者工作記憶平均分數由2.6 增加至2.9 分， 為邊緣性顯著（p=0.05），服用肉桂者工作記憶前後測平均分數沒有顯著差異。工作記憶 分數之改善與胰島素阻抗呈負相關 （r=-0.418, p<0.01），但與阿茲海默症之相關生物標記 無顯著相關。複迴歸分析結果顯示服用薑黃、BMI 及胰島素阻抗為工作記憶分數最佳預測 因子。結論：本研究觀察到的薑黃改善認知效果，可能並非透過假設之降血糖途徑或降低 生物標記基因表現量而來，推測薑黃有其他保護神經元機制。

Topics: Aged; Alzheimer Disease; Biomarkers; Blood Glucose; Body Mass Index; Bread; Cinnamomum zeylanicum; Curcuma; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Male; Memory; Middle Aged; Phytotherapy; Placebos; Plant Preparations; Postprandial Period; Prediabetic State

We previously found that curcuminoids decreased blood glucose and improved insulin resistance by reducing serum free fatty acids (FFAs) and increasing fatty acid oxidation in skeletal muscle of diabetic rats. This study was to investigate whether curcuminoids have beneficial effects on type 2 diabetic patients, and its possible mechanisms.. Overweight/obese type 2 diabetic patients (BMI ≥ 24.0; fasting blood glucose ≥ 7.0 mmol/L or postprandial blood glucose ≥11.1 mmol/L) were randomly assigned to curcuminoids (300 mg/day) or placebo for 3 months. Bodyweight, glycosylated hemoglobin A1c (HbA1c ,% ), serum fasting glucose, FFAs, lipids, and lipoprotein lipase (LPL) were determined. A total of 100 patients (curcuminoids, n = 50; placebo, n = 50) completed the trial. Curcuminoids supplementation significantly decreased fasting blood glucose (p < 0.01), HbA1c (p = 0.031), and insulin resistance index (HOMA-IR) (p < 0.01) in type 2 diabetic patients. Curcuminoids also led to a significant decrease in serum total FFAs (p < 0.01), triglycerides (P = 0.018), an increase in LPL activity (p < 0.01).. These findings suggest a glucose-lowering effect of curcuminoids in type 2 diabetes, which is partially due to decrease in serum FFAs, which may result from promoting fatty acid oxidation and utilization.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipoprotein Lipase; Male; Middle Aged; Obesity; Postprandial Period; Triglycerides; Young Adult

Numerous meta-analyses have been conducted on the effects of nutritional interventions on various health outcomes in women with polycystic ovary syndrome (PCOS). However, the strength of the evidence and its clinical significance are unclear.. This umbrella review aimed to summarize the effects of nutritional interventions on women with PCOS and assess the strength of the evidence.. PubMed, Scopus, and Web of Science were searched from inception until March 17, 2021.. Meta-analyses of randomized clinical trials (RCTs) that examined the impact of dietary modifications or supplementations on women with PCOS were selected. Data extraction, quality assessments of the meta-analyses, and evaluation of the strength of the evidence were conducted independently by 2 investigators and confirmed by a third.. Twenty-eight RCT meta-analyses were included, reporting 40 different outcomes. Lower carbohydrate, Dietary Approaches to Stop Hypertension, or lower glycemic index/load diets in women with PCOS significantly improved some anthropometric and metabolic characteristics (with very low to low certainty). Probiotics/synbiotics reduced fasting plasma glucose, fasting insulin (FI), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (with moderate to high certainty). Curcumin supplementation decreased fasting plasma glucose, FI, and HOMA-IR (with moderate certainty). Fish oil supplementation decreased FI and HOMA-IR, and omega-3 reduced triglycerides (with moderate certainty). There were also improvements in FI after taking vitamin D or inositol supplements (with moderate certainty). Supplementation with fish oil increased adiponectin (with high certainty), and probiotics/synbiotics reduced total testosterone (with moderate certainty). In subfertile women with PCOS, inositol increased the ovulation rates (with moderate certainty).. There was no high-certainty evidence that diets alone in women with PCOS improved health or reproductive outcomes. Supplementation with vitamin D, probiotics/synbiotics, omega-3, inositol, and curcumin showed favorable effects on some metabolic outcomes. Probiotics/synbiotics possibly reduces total testosterone, and inositol stimulates ovulation in women with PCOS.. PROSPERO registration no. CRD42021251496.

Topics: Blood Glucose; Curcumin; Female; Fish Oils; Humans; Inositol; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Synbiotics; Testosterone; Vitamin D

Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic β cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen

Topics: Curcumin; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Flavanones; Humans; Insulin; Insulin Resistance; Quercetin; Semaphorins

Maintaining healthy body weight is an important component of any effective diabetes management plan. However, glycemic management using insulin generally leads to weight gain. In addition, weight loss medications prescribed for diabetes management are often associated with adverse side effects, which limit their long-term usage. Alternatively, nutrition intervention provides a safe, readily accessible, and inexpensive option for diabetes management. This study describes a composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin for glycemic and weight management. Functional complementarity between berberine, cinnamaldehyde, and curcumin provides an effective means to improve insulin sensitivity without increasing adiposity. In primary human omental preadipocytes, cinnamaldehyde and curcumin additively enhance insulin-stimulated activation of Akt2 and glucose uptake, whereas berberine inhibits de novo fatty acid biosynthesis and fat cell differentiation. In a diet-induced obesity murine model, a dietary supplement with berberine, cinnamaldehyde, and curcumin prevents weight gain, improves glucose tolerance, and reduces HbA1c, blood lipids, visceral adiposity, and liver steatosis. Collectively, the composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin protects against obesity and pre-diabetic conditions in a diet-induced obesity murine model. Safety and efficacy assessment of nutrition intervention using combined berberine, cinnamaldehyde, and curcumin for glycemic and weight management in future clinical trials are warranted.

Topics: Acrolein; Animals; Berberine; Blood Glucose; Curcumin; Diabetes Mellitus; Disease Models, Animal; Fatty Acids; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Mice; Obesity; Phytochemicals; Weight Gain

To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS).. PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively.. The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05).. The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.

Topics: Animals; Cell Proliferation; Curcumin; Female; Follicle Stimulating Hormone; Glucose; Hyperandrogenism; Insulin Receptor Substrate Proteins; Insulin Resistance; Ovarian Cysts; Ovarian Neoplasms; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Polycystic Ovary Syndrome; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Testosterone

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway's molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO

Topics: Animals; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Liver; Male; Metformin; Nanoparticles; Obesity; Oxidative Stress; Rats; Streptozocin; Zinc Oxide

Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.

Topics: Animals; Bacteroidetes; Bifidobacterium; Curcumin; Diabetes Mellitus, Type 2; Diet, High-Fat; Endotoxemia; Firmicutes; Gastrointestinal Microbiome; Gene Ontology; Hyperglycemia; Insulin Resistance; Intestines; Lipopolysaccharides; Metabolomics; Mice; NF-kappa B; Rats; Signal Transduction; Tight Junction Proteins; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Curcumin (Cur) has a beneficial role in preventing metabolic dysfunctions; however, the underlying mechanism are not yet fully understood. The aim of this study was to evaluate whether the beneficial metabolic effects of curcumin are associated with the regulation of energy metabolism and activation of fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin.. We used cellular and molecular techniques to investigate the effects of Cur on C57 BL/6 mice that were fed either a control diet or a high-fat diet (HFD) with or without 0.2% Cur for 10 wk. Factors involved in energy metabolism, inflammatory responses, and insulin signaling, as well as the involvement of FNDC5/irisin pathway, were assessed.. Cur alleviated adiposity and suppressed inflammatory response in white adipose tissue (WAT) of HFD mice. Meanwhile, Cur administration increased plasma irisin concentration and improved insulin sensitivity of HFD mice. Cur increased the oxygen consumption and heat production and reduced respiratory exchange ratio (RES) in HFD mice, which were accompanied by the enhancement of metabolic activity in brown fat and inguinal WAT. Additionally, the improvement of basal metabolic rate by Cur may be partly regulated by the FNDC5/ p38 mitogen-activated protein kinase (p38 MAPK)/extracellular signal-related kinase (ERK) 1/2 pathway.. These findings demonstrated that dietary Cur alleviated diet-induced adiposity by improving insulin sensitivity and whole body energy metabolism via the FNDC5/p38 MAPK/ERK pathways.

Topics: Animals; Curcumin; Diet, High-Fat; Energy Metabolism; Fibronectins; Insulin Resistance; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal

Curcumin (CUR) is the active ingredient of Traditional Chinese Medicine turmeric (Curcuma longa L.), which has been used for treatment of diabetes in Ayurveda and China. CUR exerts potent anti-insulin-resistant effects in various cell lines. However, previous studies indicated CUR was metabolized extensively in vivo and massively degraded in a medium alkaline buffer solution. The real active component of the anti-insulin-resistant activity of CUR in vitro is not clear.. Our study identified the functional contribution of the metabolites of CUR and the related molecular mechanism in improving insulin sensitivity.. HPLC and UPLC-QQQ-MS analyses were used to investigate the stability and metabolism of CUR in HepG2 cells. The effect of the metabolic products of CUR on insulin sensitivity was evaluated in high glucose (HG)-induced insulin-resistant HepG2 cells. A network pharmacology approach was used to examine the potential targets of the metabolites, and Western blotting was performed to verify changes in the targets.. CUR was unstable in the cell culture medium, but the prototypes, metabolites and degradation products of CUR coexisted in the HepG2 cell culture experiment. The insulin sensitivity assay demonstrated that CUR and its metabolites enhanced insulin sensitivity in HG-induced insulin-resistant HepG2 cells, but the total degradation products of CUR may not play the major role. Similar to CUR, hexahydrocurcumin (HHC) and octahydrocurcumin (OHC) improved insulin sensitivity by strengthening the PI3K-AKT-GSK3B signal and suppressing the phosphorylation of ERK/JNK in HG-induced insulin-resistant HepG2 cells.. Metabolites of CUR played a critical role in counteracting insulin resistance in HG-induced HepG2 cells. CUR exerted anti-insulin resistance effect in HepG2 cells in a multi-component, multi-target, and multi-pathway manner.

Topics: Biotransformation; Curcumin; Drug Stability; Extracellular Signal-Regulated MAP Kinases; Glucose; Glycogen Synthase Kinase 3 beta; Hep G2 Cells; Hepatocytes; Humans; Insulin; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction

Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies.. PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days.. PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased β cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels.. To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.

Topics: Animals; Curcumin; Disease Models, Animal; Female; Insulin Resistance; Nanoparticles; Pancreas; Phosphatidylinositol 3-Kinase; Polycystic Ovary Syndrome; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

Both oxidative stress and inflammation contribute to the development of insulin resistance (IR). Curcumin (Cur) not only has an anti-inflammatory effect but also has an antioxidative stress effect via the activation of NF-E2-related factor 2 (Nrf2). Since there is close cross-communication between inflammation and oxidative stress, we examined whether Cur could modulate Nrf2 function via its anti-inflammatory ability and investigated its underlying mechanism. In this study, we show that Cur inhibits inflammatory signaling and Kelch-like ECH-associated protein 1 (Keap1) expression, which is accompanied by the activation of the Nrf2 system. We further identified that the proinflammatory cytokine tumor necrosis factor alpha (TNFα) could stimulate Keap1 synthesis and increase Nrf2 polyubiquitination, but these effects could be significantly inhibited by Cur treatment. This study demonstrates that Cur-induced Nrf2 activation occurs through the inhibition of inflammatory signaling-mediated upregulation of Keap1, contributing to its beneficial effects on redox homeostasis and insulin sensitivity.

Topics: Animals; Curcumin; Diet, High-Fat; Feeding Behavior; Glucose Tolerance Test; Hep G2 Cells; Humans; Inflammation; Insulin; Insulin Resistance; Kelch-Like ECH-Associated Protein 1; Male; Mice, Inbred C57BL; NF-E2-Related Factor 2; Proteasome Endopeptidase Complex; Proteolysis; RNA, Messenger; Signal Transduction; Up-Regulation

The objective of the present study was to investigate the effect of curcumin on insulin resistance (IR) and hepatic lipid accumulation in intra-uterine growth restriction (IUGR). Rats with a normal birth weight (NBW) or IUGR were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NBW-C and IUGR-C groups) from 6 to 12 weeks. Rats in the IUGR group showed higher levels of glucose and homeostasis model assessment for insulin resistance index (HOMA-IR) (P < 0·05) than in the NBW group. The livers of IUGR rats exhibited higher (P < 0·05) concentration of TAG and lower (P < 0·05) activities of lipolysis enzymes compared with the normal rats. In response to dietary curcumin supplementation, concentrations of serum insulin, glucose and HOMA-IR, pyruvate, TAG, total cholesterol and NEFA in the liver were decreased (P < 0·05). The concentrations of glycogen and activities of lipolysis enzymes in the liver were increased (P < 0·05) in the IUGR-C group compared with the IUGR group. These results were associated with lower (P < 0·05) phosphorylated insulin receptor substrate 1, protein kinase B or Akt, glycogen synthase kinase 3β and expressions of sterol regulatory element binding protein 1 and fatty acid synthase (FASN); decreased expressions for Cd36, sterol regulatory element binding protein 1c (Srebf1) and Fasn; increased (P < 0·05) expression of PPARα; and expressions for Ppara and hormone-sensitive lipase in the liver of IUGR-C rats than the IUGR rats. Maternal malnutrition caused IR and lipid accumulation in the liver. Curcumin supplementation prevented IR by regulating insulin signalling pathways and attenuated hepatic lipid accumulation.

Topics: Animals; Curcumin; Disease Models, Animal; Female; Fetal Growth Retardation; Gene Expression; Insulin; Insulin Resistance; Lipid Metabolism; Lipolysis; Liver; Liver Glycogen; Pregnancy; Rats; Rats, Sprague-Dawley; Signal Transduction; Sterol Regulatory Element Binding Proteins

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic macrophage inflammation, steatosis and fibrosis. Liposomes injected intravenously passively target hepatic myeloid cells and have potential to deliver immunomodulatory compounds and treat disease. We investigated targeting, delivery, immunomodulation and efficacy of liposomes in mice with diet-induced NASH.. Liposome-encapsulated lipophilic curcumin or 1,25-dihydroxy-vitamin D3 (calcitriol) were injected intravenously into mice with diet-induced NASH. Liver and cell liposome uptake was assessed by in vivo imaging and flow cytometry. Immunomodulation of targeted cells were assessed by RNA transcriptome sequencing. NASH was assessed by histological scoring, serum liver enzymes and fasting glucose/insulin and liver RNA transcriptome sequencing.. Liposomes targeted lipid containing MHC class-II. Liposomes are a new strategy to target lipid rich inflammatory dendritic cells and have potential to deliver immunomodulatory compounds to treat NASH.

Topics: Animals; Curcumin; Diet, High-Fat; Disease Progression; Female; Fibrosis; Hepatocytes; Immunologic Factors; Inflammation; Insulin Resistance; Liposomes; Liver; Liver Cirrhosis; Macrophages; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Transcriptome; Vitamin D

Curcumin is a well‑known phenolic substance and has many pharmacological effects associated with metabolism. However, the exact molecular mechanisms underlying this process have yet to be determined. The Notch pathway is a signal transduction pathway involved in energy metabolism. The present study aimed to investigate the effects of curcumin administration on glucose‑lipid metabolism in rats subjected to a high fat diet, and investigate changes in Notch‑1 signaling. Sprague‑Dawley rats (n=40) were randomly divided into four groups (10 rats/group): Control diet group, high fat diet group, high fat diet plus curcumin low dose group and high fat diet plus curcumin high dose group. Following 8 weeks of treatment with curcumin (100 mg/kg in the low dose group and 200 mg/kg in the high dose group), serum metabolic markers and hepatic gene expression patterns were investigated. No differences in body weight following 8 weeks of curcumin administration (P>0.05) were observed; however, curcumin treatment did reduce visceral fat levels (peri‑epididymal and peri‑renal), and decreased cholesterol, triglyceride and low‑density lipoprotein levels in serum compared with the high fat diet rats that did not receive curcumin (P<0.05, P<0.01). An oral glucose tolerance test and an intraperitoneal insulin tolerance test revealed that insulin resistance was reduced (P<0.05 or P<0.01) and tissue section analysis revealed that hepatosteatosis was attenuated following treatment with curcumin. Furthermore, the protein expression of Notch‑1 and its downstream target Hes‑1 were suppressed. These effects were also in parallel with an upregulation of fatty acid oxidation‑associated gene expression, including peroxisome proliferator‑activated receptor (PPAR)‑α, carnitine palmitoyltransferase 1 and PPAR‑γ (P<0.05). In addition, curcumin administration led to a downregulation in the expression of lipogenic genes, including sterol regulatory element‑binding protein, fatty acid synthase and acetyl‑CoA carboxylase (P<0.05). The expression of inflammation‑associated genes, including nuclear factor‑κB, tumor necrosis factor‑α and prostaglandin‑endoperoxide synthase 2 were also suppressed. The results of the present study suggest that the hepatic Notch‑1 pathway can be suppressed via curcumin treatment, which may ameliorate fatty liver and insulin resistance in rats subjected to a high fat diet.

Topics: Animals; Blood Glucose; Body Weight; Curcumin; Disease Models, Animal; Fatty Liver; Insulin Resistance; Intra-Abdominal Fat; Lipid Metabolism; Liver; Male; Models, Biological; Organ Size; Rats; Receptor, Notch1; Signal Transduction

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biomarkers; C-Reactive Protein; Cholesterol; Curcumin; Diet, High-Fat; Dietary Sucrose; Endothelium, Vascular; Homocysteine; Inflammation; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Liver; Male; Malondialdehyde; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Risk Factors; Vascular Cell Adhesion Molecule-1; Vascular Diseases

To examine whether curcumin has protective effect on insulin resistance induced by bisphenol A (BPA) in LO2 cells and whether this effect was mediated by inhibiting the inflammatory mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways.. LO2 cells were stimulated with BPA in the presence or absence of curcumin for 5 days. Glucose consumption, activation of insulin signaling, MAPKs and NF-κB pathways, levels of inflammatory cytokines and MDA production were analyzed.. Curcumin prevented BPA-induced reduction of glucose consumption and suppression of insulin signaling pathway, indicating curcumin alleviated BPA-triggered insulin resistance in LO2 cells. mRNA and proteins levels of TNF-α and IL-6, as well as MDA level in LO2 cells treated with BPA were decreased by curcumin. Furthermore, curcumin downregulated the activation of p38, JNK, and NF-κB pathways upon stimulation with BPA. Inhibition of JNK pathway, but not p38 nor NF-κB pathway, improved glucose consumption and insulin signaling in BPA-treated LO2 cells.. Curcumin inhibits BPA-induced insulin resistance by suppressing JNK pathway.

Topics: Anthracenes; Benzhydryl Compounds; Cell Line; Curcumin; Enzyme Activation; Humans; Imidazoles; Inflammation; Insulin Resistance; MAP Kinase Signaling System; NF-kappa B; Oxidative Stress; Phenols; Pyridines; Pyrrolidines; Thiocarbamates

Curcumin is a polyphenol compound with many pharmacological activities including antioxidant, lipid-loweing and liver protective. Dihydrocurcumin (DHC) is one of the major metabolites of curcumin. So far, the pharmacological activity of DHC has not been reported. Here, we evaluate the effects of DHC on oleic acid (OA)-induced lipid accumulation, oxidative stress and insulin resistance and the underlying mechanism in L02 and HepG2 cells.. OA-induced L02 and HepG2 cells were used as the in vitro model of nonalcoholic fatty liver disease (NAFLD). Lipid accumulation, oxidative stress, glucose uptake and cell inflammation were evaluated by cellular biochemical assay, respectively. Signaling pathways involved in lipid metabolism including peroxisome proliferator activated receptor-α (PPARα), the sterol regulatory element binding protein-1C (SREBP-1C) and patatin-like phospholipase domain containing 3 (PNPLA3), glucose uptake including phosphatidylinositol 3-kinase (PI3K) and phosphorylated serine-threonine protein kinase (pAKT), and oxidative stress including nuclear factor E2-related factor 2 (Nrf2), cytochrome P450 4A (CYP4A) and 2E1 (CYP2E1) were investigated by western blotting and RT-qPCR, respectively.. DHC decreased the levels of cellular triglycerides (TG) by regulating the mRNA and protein expression levels of SREBP-1C, PNPLA3 and PPARα. At the same time, DHC improved the hepatocellular glucose uptake by increasing the protein expression levels of pAKT and PI3K. Furthermore, DHC reduced the levels of cellular NO and ROS via Nrf2 signaling pathways.. The present study firstly revealed that DHC ameliorated OA-induced steatosis through regulating the lipid metabolism, oxidative stress and insulin resistance in HepG2 and L02 cells.

Topics: Cell Death; Cell Survival; Curcumin; Gene Expression Regulation; Glucose; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Nitric Oxide; Oleic Acid; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; RNA, Messenger; Signal Transduction; Triglycerides

Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham+Cur group and BDL+Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signal-regulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1α (HIF-1α) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1α and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0·05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P<0·05), indicating return of these parameters towards normalcy. In conclusion, Curcumin showed hepatoprotective activity against BDL-induced liver injury and hepatic insulin resistance by influencing the expression of some genes/proteins involved in these processes, and the results suggest that it can be used as a therapeutic option.

Topics: Animals; Bile Ducts; Curcumin; Gene Expression Profiling; Homeostasis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Insulin Receptor Substrate Proteins; Insulin Resistance; Ligation; Liver Cirrhosis; Male; Malondialdehyde; Mitogen-Activated Protein Kinase 3; NADPH Oxidase 1; rac1 GTP-Binding Protein; Rats; Rats, Wistar; STAT3 Transcription Factor

Elevated levels of free fatty acids (FFAs) in the liver, resulting from either increased lipolysis or imbalanced FFAs flux, is a key pathogenic factor of hepatic steatosis. This study was conducted to examine the therapeutic effect of tetrahydrocurcumin (THC), a naturally occurring curcuminoid and a metabolite of curcumin, on oleic acid (OA)-induced steatosis in human hepatocellular carcinoma cells and to elucidate the underlying mechanism. HepG2 cells were incubated with OA to induce steatosis, and then treated with various concentrations of THC. The results showed that THC treatment significantly decreased lipid accumulation in OA-treated HepG2 cells, possibly, by inhibiting the expression of the lipogenic proteins, sterol regulatory element-binding protein 1 (SREBP-1c), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4). Moreover, THC attenuated OA-induced hepatic lipogenesis in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner, which was reversed by pretreatment with an AMPK inhibitor. THC promoted lipolysis and upregulated the expression of genes involved in β-oxidation. Glucose uptake and insulin signaling impaired in HepG2 cells incubated with OA were abated by THC treatment, including phosphorylation of the insulin receptor substrate 1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Akt and downstream signaling pathways, forkhead box protein O1 (FOXO1) and glycogen synthase kinase 3 β (GSK3β), which are involved in gluconeogenesis and glycogen synthesis, respectively. Altogether, these results demonstrated the novel therapeutic benefit of THC against hepatic steatosis and, consequently, a potential treatment for non-alcoholic fatty liver disease (NAFLD).

Topics: Curcumin; Fatty Acid-Binding Proteins; Fatty Acids, Nonesterified; Fatty Liver; Glucose; Hep G2 Cells; Humans; Insulin Resistance; Lipogenesis; Oleic Acid; PPAR alpha; Sterol Regulatory Element Binding Protein 1

Salidroside and curcumin (SC) formula could alleviate lipid deposition in high fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the mechanisms are still unknown, and the magnitude of potential therapeutic benefit remains understudied.. The rats were treated with high fat diet for 14 weeks to induce NAFLD. The experiment was divided into control, model (NAFLD), SC formula and rosiglitazone groups (n = 7 in each group). Hematoxylin-eosin (H&E) staining was applied to detect liver morphological changes. Biochemical, metabolic indices and inflammation factors in liver tissue and serum were detected. Additionally, the activities of related enzymes were detected by enzyme-linked immunosorbent assay.. In the established rat model, typical lipid deposition and liver steatosis were observed. Liver triglyceride, free fatty acids, sera alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fasting insulin, fasting blood glucose and homeostasis model assessment of insulin resistance were elevated in model group. Liver malondialdehyde was significantly elevated, while superoxide dismutase was significantly decreased in model group, compared with control. Moreover, tumor necrosis factor-α and Interleukin-1 were significantly produced in model group, compared with control. As a mechanism, high fat diet decreased tissue AMP-activated protein kinase (AMPK), phosphorylated AMPK, carnitine palmitoyltransferase 1 and increased inacetyl-CoA carboxylase (ACCase), phosphorylated ACCase. Importantly, these abnormal changes caused by high fat diet were reduced by SC formula administration.. SC formula could ameliorate the injury caused by high fat diet. The effect was likely mediated via its influence on insulin resistance, lipid peroxidation injury and AMPK signaling pathway.

Topics: AMP-Activated Protein Kinases; Animals; Biomarkers; Blood Glucose; Curcumin; Diet, High-Fat; Disease Models, Animal; Drug Combinations; Glucosides; Insulin; Insulin Resistance; Lipid Metabolism; Lipid Peroxidation; Liver; Male; Non-alcoholic Fatty Liver Disease; Phenols; Rats, Sprague-Dawley; Signal Transduction

Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

Topics: Animals; Behavior, Animal; Blood Glucose; Corticosterone; Curcumin; Depression; Disease Models, Animal; Glucagon; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Male; Pioglitazone; Rats; Rats, Sprague-Dawley; Stress, Psychological; Thiazolidinediones

The role of phytochemicals in general well-being has been recognized. Curcumin is an ideal example. Hypoxia in adipose tissue is a major cause of inflammation and insulin resistance in obesity. Herein we mainly explored inflammation, insulin resistance and angiogenesis in 3T3-L1 adipocytes and possible reversal with the curcumin during hypoxia. Hypoxia for 24h significantly increased (P ≤ 0.05) the secretion of monocyte chemotactic protein-1 (4.59 fold), leptin (2.96 fold) and reduced adiponectin (2.93 fold). mRNA level of resistin (6.8 fold) and toll-like receptor-4 (TLR-4) (8.8 fold) was upregulated. Increased serine phosphorylation of insulin receptor substrate 1 (IRS-1) (1.9 fold) and decreased expression of insulin receptor substrate 2 (IRS-2) (0.53 fold) in hypoxic group were observed. Hypoxia significantly increased (P ≤ 0.05) basal glucose uptake (3.3 fold), GLUT-1 expression and angiogenic factors but down regulated GLUT-4. Curcumin protected adipocytes from hypoxia induced inflammation and insulin resistance via reducing inflammatory adipokine, nuclear factor-κB (NF-κB)/c-jun N-terminal kinase (JNK) and serine phosphorylation of IRS-1 receptors and improving adiponectin secretion.

Topics: 3T3-L1 Cells; Active Transport, Cell Nucleus; Adipocytes; Animals; Biomarkers; Cell Hypoxia; Cell Nucleus; Curcumin; Cytokines; Enzyme Activation; Gene Expression Regulation; Glucose Transporter Type 1; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Mice; Toll-Like Receptor 4; Transcription Factor RelA

Weight regain, adipose tissue growth, and insulin resistance can occur within days after the cessation of regular dieting and exercise. This phenomenon has been attributed, in part, to the actions of stress hormones as well as local and systemic inflammation. We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). Sprague-Dawley rats (6-7 wk old) underwent a "training" protocol of 24-h voluntary running wheel access and CR (15-20 g/day; ~50-65% of ad libitum intake) for 3 wk ("All Trained") or were sedentary and fed ad libitum ("Sed"). After 3 wk, All Trained were randomly divided into one group which was terminated immediately ("Trained"), and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked groups received either a daily gavage of a placebo ("Detrained + Placebo") or curcumin (200 mg/kg) ("Detrained + Curcumin"). Cessation of daily CR and exercise caused an increase in body mass, as well as a 9- to 14-fold increase in epididymal, perirenal, and inguinal adipose tissue mass, all of which were attenuated by curcumin ( P < 0.05). Insulin area under the curve (AUC) during an oral glucose tolerance test, HOMA-IR, and C-reactive protein (CRP) were elevated 6-, 9-, and 2-fold, respectively, in the Detrained + Placebo group vs. the Trained group (all P < 0.05). Curcumin reduced insulin AUC, HOMA-IR, and CRP vs. the placebo group (all P < 0.05). Our results indicate that curcumin has a protective effect against weight regain and impaired metabolic control following a successful period of weight loss through diet and exercise, perhaps via inhibition of glucocorticoid action and inflammation. NEW & NOTEWORTHY Weight regain after dieting and exercise is a common phenomenon plaguing many individuals. The biological mechanisms underlying weight regain are incompletely understood and are likely multifactorial. In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipose Tissue; Animals; Caloric Restriction; Corticosterone; Curcumin; Diet; Glucose Intolerance; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Muscle, Skeletal; Obesity; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Sprague-Dawley; Weight Gain

Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemicals. Accumulating evidence indicates that exposure to BPA contributes to insulin resistance through diverse mechanism including inflammation and oxidative stress. Previous studies have suggested curcumin as a safe phytochemical which can improve obesity-related insulin resistance, inflammation and oxidative stress. The present study aimed to investigate the ability of curcumin to prevent BPA-induced insulin resistance in vitro and the underlying mechanism. Following the establishmet of in vitro insulin resistance via BPA treatment in human liver HepG2 cells, the protective effects of curcumin were determiend. We showed that treatment of HepG2 cells with 100nM BPA for 5days induced significantly decreased glucose consumption, impaired insulin signaling, elevation of pro-inflammatory cytokines and oxidative stress, and activation of signaling pathways; inhibition of JNK and p38 pathways, but not ERK nor NF-κB pathways, improved glucose consumption and insulin signaling in BPA-treated HepG2 cells. Moreover, we revealed that curcumin effectively attenuated the spectrum of effects of BPA-triggered insulin resistance, whereas pretreatment with JNK and p38 agonist anisomycin could significantly compensate the effects caused by curcumin. These data illustrated the role of JNK/p38 activation in BPA-induced insulin resistance and suggested curcumin as a promising candidate for the intervention of BPA-induced insulin resistance.

Topics: Antioxidants; Benzhydryl Compounds; Cell Survival; Curcumin; Endocrine Disruptors; Glucose; Hep G2 Cells; Humans; Insulin Resistance; Lipid Peroxidation; MAP Kinase Signaling System; Oxidative Stress; Phenols

Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti-tumorigenic properties that is beneficial in defending against NASH and was recently proved to be an Nrf2 activator. The aim of this study was to evaluate whether Nrf2 activation could be involved in NASH mitigation by curcumin.. Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2 protein expression were explored in adult Sprague-Dawley rats developing high-fat-diet-induced NASH and submitted to curcumin gavage for 6 weeks.. Curcumin administration led to lower degrees of hepatic steatosis and inflammation; lower levels of serum aminotransferases, lipids, and homeostasis model assessment of insulin resistance; and lower serum and hepatic contents of tumor necrosis factor-α (TNF-α), interleukin-6, and malondialdehyde. In contrast, higher hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei was significantly higher in rats with curcumin.. Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.

Topics: Animals; Antioxidants; Curcumin; Diet, High-Fat; Fatty Liver; Heme Oxygenase-1; Insulin Resistance; Male; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Fructose; Glucose Intolerance; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Oxidative Stress; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Wistar; Structure-Activity Relationship

The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats.. Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment.. High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition.. Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Curcumin; Diet, High-Fat; Dietary Supplements; Fasting; Inflammation; Inflammation Mediators; Insulin; Insulin Resistance; Liver; Male; Muscle, Skeletal; Obesity; Oxidative Stress; Rats; Rats, Wistar; Triglycerides

Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Lepr(db/db) on the Kaliss background).. In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity.. These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance.

Topics: 3T3-L1 Cells; Animals; Body Composition; Cell Survival; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Homeostasis; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; Obesity; Oligopeptides; Pentacyclic Triterpenes; Polyphenols; Proteasome Inhibitors; Receptors, Leptin; Triterpenes

Previous study has shown that curcumin directly or indirectly suppresses insulin signaling in 3T3-L1 adipocytes. However, the underlying mechanism remains unclear. Here we experimentally demonstrate that curcumin inhibited the ubiquitin-proteasome system (UPS) function, activated autophagy, and reduced protein levels of protein kinase B (Akt) in a dose- and time-dependent manner in 3T3-L1 adipocytes, accompanied with attenuation of insulin-stimulated Akt phosphorylation, plasma membrane translocation of glucose transporter type 4 (GLUT4), and glucose uptake. These in vitro inhibitory effects of curcumin on Akt protein expression and insulin action were reversed by pharmacological and genetic inhibition of autophagy but not by inhibition of the UPS and caspases. In addition, Akt reduction in adipose tissues of mice treated with curcumin could be recovered by administration of autophagy inhibitor bafilomycin A1 (BFA). This new finding provides a novel mechanism by which curcumin induces insulin resistance in adipocytes.

Topics: Adipocytes; Adipose Tissue; Animals; Autophagy; Autophagy-Related Protein 5; Caspase Inhibitors; Caspases; Curcumin; Enzyme Stability; Gene Knockdown Techniques; Insulin Resistance; Mice, Inbred C57BL; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proteolysis; Proto-Oncogene Proteins c-akt; Signal Transduction; Ubiquitin

Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.

Topics: Adipose Tissue; Animals; Blood Glucose; Cholesterol; Curcumin; Diabetes Mellitus, Type 2; Diet, High-Fat; Down-Regulation; Energy Metabolism; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Sterol Regulatory Element Binding Proteins; Triglycerides; Weight Gain

Curcumin is natural polyphenol with beneficial effects on lipid and glucose metabolism and this study aimed to investigate the effects of curcumin on lipolysis and hepatic insulin resistance. Endoplasmic reticulum (ER) stress and lipolysis signaling in adipose and FFA influx, lipid deposits, and glucose production in liver were examined. Palmitate challenge and high-fat diet feeding evoked ER stress-associated lipolysis with cAMP accumulation in adipose tissue. Curcumin treatment inhibited adipose tissue ER stress by dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α and reduced cAMP accumulation by preserving phosphodiesterase 3B induction. Knockdown of mitogen-activated protein kinase α1/2α with siRNAs diminished such effects of curcumin. As a result from downregulation of cAMP, curcumin blocked protein kinase (PK)A/hormone-sensitive lipase lipolysis signaling, and thereby reduced glycerol and FFA release from adipose tissue. Curcumin reduced FFA influx into the liver by blocking FFA trafficking, and then prevented diacylglycerol deposits and PKCε translocation in the liver, resultantly improving insulin action in the suppression of hepatic gluconeogenesis. Curcumin decreased adipose lipolysis by attenuating ER stress through the cAMP/PKA pathway, reduced FFA influx into the liver by blocking FFA trafficking, and thereby improved insulin sensitivity to inhibit hepatic glucose production. These findings suggested a novel pathway of curcumin to prevent lipid deposits and insulin resistance in liver by beneficial regulation of adipose function.

Topics: Adipocytes; Adipose Tissue; Animals; Curcumin; Diet, High-Fat; Endoplasmic Reticulum Stress; Fatty Acids, Nonesterified; Glucose; Humans; Insulin Resistance; Lipase; Lipid Metabolism; Lipolysis; Liver; Mice; Phosphorylation; Signal Transduction

KBH-1 is an herbal mixture of Saururus chinensis, Curcuma longa and Polygala tenuifolia. Each herb has been reported to have various pharmaceutical activities; however, the synergistic effect of this herbal composition on obesity has not yet been determined. We investigated the alleviation effect of KBH-1 and its possible molecular mechanism in obesity-induced hepatic steatosis and leptin resistance in the hypothalamus.. We used HepG2 cells, primary neuronal cells and a high-fat diet (HFD)-induced obesity rat model to determine the effect of KBH-1 in vitro and in vivo on hepatic steatosis and leptin resistance accompanied by obesity. To identify the alleviation effect on lipid accumulation, HepG2 cells stimulated by FFA were stained with Oil Red O; in addition, immunoblotting and qPCR were performed to determine the effect of KBH-1 on the activation of proteins and nuclear enzymes in HepG2 cells and the steatotic liver of HFD-induced obesity rats. To examine the effect of KBH-1 on the leptin resistance of the hypothalamus and its possible molecular mechanism, we examined the effect of KBH-1 on the activation of the leptin resistance-related protein in primary cultured cortical neuron cells and the hypothalamus of an HFD-induced obesity rat model. In addition, we used HPLC analysis to identify the standard compound of KBH-1.. KBH-1 not only suppressed the lipid deposition in HepG2 cells exposed to free fatty acids (FFA) but also significantly down-regulated major factors in lipogenesis and up-regulated major factors in lipolysis. Similarly, in a HFD-induced obesity model, KBH-1 improved hepatic steatosis by alleviating the effects on lipogenic genes and kinases. In addition, KBH-1 significantly improved the leptin-mediated signals impaired by obesity or FFA in the obesity model and primary cultured cortical neuron cells. In addition, KBH-1 was analyzed to include six standard compounds using HPLC analysis, among these compounds, onji-saponin B and curcumin were potently suppressed the level of triglycerides.. KBH-1 exhibits alleviating effects by improving hepatic steatosis and leptin resistance by up-regulating the activation of AMPK and suppressing the expression of PPARγ. These findings show the potential of KBH-1 as a functional food supplement or preventive agent in the treatment of obesity.

Topics: Animals; Curcuma; Diet, High-Fat; Drugs, Chinese Herbal; Fatty Liver; Hep G2 Cells; Humans; Insulin Resistance; Leptin; Male; Polygala; Rats; Rats, Sprague-Dawley; Saururaceae

Curcumin is a yellow pigment isolated from Corcuma longan. This research investigates the improvement of curcumin on INS-1 cells with insulin resistance induced by high glucose. INS-1 cells were treated with high glucose (30 mmol L(-1)) for 48 h. Subsequently, the medium was replaced with curcumin for 24 h. Curcumin effectively increased insulin gene expression and glucose stimulated insulin secretion (GSIS) in a dose-dependent manner. Furthermore, the molecular mechanism of curcumin-induced insulin expression and secretion in high glucose-induced INS-1 cells was investigated in this study. Curcumin increased the expression of glucose transporter 2 (GLUT2) and phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1), phosphatidylinositol-3-kinase (PI3K) and AKT in the INS-1 cells. Moreover, curcumin stimulation increased the expression of PDX-1 and GCK. This investigation suggests that curcumin prevented high glucose-reduced insulin expression and secretion through activation of the PI3K/Akt/GLUT2 pathway in INS-1 cells.

Topics: Animals; Cell Line; Cell Survival; Curcumin; Glucokinase; Glucose; Glucose Transporter Type 2; Homeodomain Proteins; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Receptor, Insulin; RNA, Messenger; Trans-Activators; Up-Regulation

Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin.

Topics: Analgesics; Animals; Curcumin; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ganglia, Spinal; Insulin Resistance; Male; Neuralgia; Neurons; Pain Threshold; Rats, Sprague-Dawley; Sodium Channels; Tetrodotoxin

Long-term dietary curcumin (>12 wk) improves metabolic homeostasis in obese mice by sensitizing insulin signaling and reducing hepatic gluconeogenesis. Whether these occur only secondary to its chronic anti-inflammatory and antioxidative functions is unknown.. In this study, we assessed the insulin sensitization effect of short-term curcumin gavage in a rapid dexamethasone-induced insulin resistance mouse model, in which the chronic anti-inflammatory function is eliminated.. Six-week-old male C57BL/6 mice received an intraperitoneal injection of dexamethasone (100 mg/kg body weight) or phosphate-buffered saline every day for 5 d, with or without simultaneous curcumin gavage (500 mg/kg body weight). On day 7, insulin tolerance tests were performed. After a booster dexamethasone injection and curcumin gavage on day 8, blood glucose and insulin concentrations were measured. Liver tissues were collected on day 10 for quantitative polymerase chain reaction and Western blotting to assess gluconeogenic gene expression, insulin signaling, and the expression of fibroblast growth factor 21 (FGF21). Primary hepatocytes from separate, untreated C57BL/6 mice were used for testing the in vitro effect of curcumin treatment.. Dexamethasone injection impaired insulin tolerance (P < 0.05) and elevated ambient plasma insulin concentrations by ~2.7-fold (P < 0.01). Concomitant curcumin administration improved insulin sensitivity and reduced hepatic gluconeogenic gene expression. The insulin sensitization effect of curcumin was demonstrated by increased stimulation of S473 phosphorylation of protein kinase B (P < 0.01) in the dexamethasone-treated mouse liver, as well as the repression of glucose production in primary hepatocytes (P < 0.001). Finally, curcumin gavage increased FGF21 expression by 2.1-fold in the mouse liver (P < 0.05) and curcumin treatment increased FGF21 expression in primary hepatocytes.. These observations suggest that the early beneficial effect of curcumin intervention in dexamethasone-treated mice is the sensitization of insulin signaling, involving the stimulation of FGF21 production, a known insulin sensitizer.

Topics: Animals; Antioxidants; Blood Glucose; Cells, Cultured; Curcumin; Dexamethasone; Dietary Supplements; Fibroblast Growth Factors; Gene Expression Regulation, Enzymologic; Glucocorticoids; Gluconeogenesis; Hep G2 Cells; Humans; Insulin; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Prediabetic State; Random Allocation; Recombinant Proteins; Signal Transduction

Fructose consumption can induce insulin resistance and metabolic syndrome, which are associated with glomerular podocyte dysfunction and proteinuria. This study investigated whether fructose caused insulin signaling impairment in podocyte dysfunction and injury, and whether curcumin reduced these disturbances.. Rats were fed with 10% fructose for 6 weeks and then orally cotreated with curcumin for next 6 weeks. Metabolic syndrome, podocyte injury, microRNA expression, and insulin signaling were evaluated. Curcumin significantly alleviated fructose-induced podocyte injury and proteinuria, miR-206 low-expression, protein tyrosine phosphatase 1B (PTP1B) overexpression, as well as downregulation of insulin receptor, insulin receptor substrate 1, caveolin-1, protein kinase B, and extracellular signal-regulated kinases 1 and 2 phosphorylation in kidney cortex or glomeruli of fructose-fed rats. These effects were further confirmed in cultured differentiated podocytes exposed to 5 mM fructose in the presence or absence of curcumin, PTP1B siRNA, lentivirus-mediated PTP1B recombinant overexpression, miR-206 mimic, or miR-206 inhibitor transfection, showing that miR-206 upregulation may contribute to improve insulin signaling through regulating PTP1B expression.. Curcumin is suggested to activate miR-206 expression to downregulate PTP1B, and then improve insulin signaling, protect against fructose-induced glomerular podocyte injury, and proteinuria, which may provide new evidence regarding curcumin's effects on fructose-associated podocyte injury.

Topics: Animals; Curcumin; Fructose; Gene Expression Regulation; Insulin; Insulin Resistance; Male; Metabolic Syndrome; MicroRNAs; Podocytes; Protective Agents; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proteinuria; Rats, Sprague-Dawley; Up-Regulation

The use of biocompounds as agents with potential anti-obesity effects might be a feasible alternative to the prescription of traditional drugs in the near future. The goal of the present study was to screen five different compounds in relation to their ability to prevent body weight gain and ameliorate obesity-associated metabolic impairments, namely insulin resistance. For this purpose, seventy Wistar rats were randomly assigned into seven experimental groups. A standard diet-fed control group (control, n=10); a high-fat, high-sucrose diet-fed group (HFS, n=10) and five experimental groups which were fed the HFS diet supplemented with one of the following biocompounds; curcumin (100 mg/kg bw, n=10), chlorogenic acid (50 mg/kg bw, n=10), coumaric acid (100 mg/kg bw, n=10), naringin (100 mg/kg bw, n=10) and leucine (1% of diet, n=10). These results confirm the effectiveness of all the compounds to reduce significantly food efficiency, despite the significant higher food intake. Moreover, visceral fat mass percentage was significantly decreased after naringin and coumaric acid supplementation. In fact, this finding might be related to the considerable amelioration of HOMA-IR index detected in naringin-treated animals. A significant reduction in serum insulin levels and an improvement in the intraperitoneal glucose tolerance test and AUC were found in leucine- and coumaric acid-treated rats, respectively. In summary, the tested biocompounds, particularly naringin, coumaric acid and leucine, showed potential benefits in the prevention of obesity-related complications in rats, at least at the proved doses.

Topics: Animals; Blood Glucose; Chlorogenic Acid; Coumaric Acids; Curcumin; Diet, High-Fat; Dietary Fats; Dietary Supplements; Flavanones; Humans; Insulin Resistance; Leucine; Male; Obesity; Rats; Rats, Wistar; Sucrose

Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications.. Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals.. Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism.. High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings.

Topics: Animals; Blood Glucose; Cricetinae; Curcuma; Diet, High-Fat; Gene Expression Regulation; Humans; Hyperglycemia; Insulin; Insulin Resistance; Lipid Peroxidation; Liver; Mesocricetus; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Plant Extracts; Platelet Aggregation; Rats; Sterol Regulatory Element Binding Protein 1; Thrombosis; Transcription Factors

Type 2 diabetes is growing at epidemic proportions, and pharmacological interventions are being actively sought. This study examined the effect of a novel neuroprotective curcuminoid, CNB-001 [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl)vinyl)-2-methoxy-phenol], on glucose intolerance and insulin signaling in high-fat diet (HFD)-fed mice. C57BL6 mice (5-6 weeks old) were randomly assigned to receive either a HFD (45% fat) or a low-fat diet (LFD, 10% fat) for 24 weeks, together with CNB-001 (40 mg/kg i.p. per day). Glucose tolerance test revealed that the area under the curve of postchallenge glucose concentration was elevated on HF-feeding, which was attenuated by CNB-001. CNB-001 attenuated body weight gain, serum triglycerides, and IL-6, and augmented insulin signaling [elevated phosphoprotein kinase B (p-Akt), and phosphoinsulin receptor (p-IR)β, lowered endoplasmic reticulum (ER) stress, protein-tyrosine phosphatase 1B (PTP1B)] and glucose uptake in gastrocnemius muscle of HFD-fed mice. Respiratory quotient, measured using a metabolic chamber, was elevated in HFD-fed mice, which was unaltered by CNB-001, although CNB-001 treatment resulted in higher energy expenditure. In cultured myotubes, CNB-001 reversed palmitate-induced impairment of insulin signaling and glucose uptake. Docking studies suggest a potential interaction between CNB-001 and PTP1B. Taken together, CNB-001 alleviates obesity-induced glucose intolerance and represents a potential candidate for further development as an antidiabetic agent.

Topics: Adiposity; Animals; Catalytic Domain; Cell Line; Cell Survival; Curcumin; Dietary Fats; Endoplasmic Reticulum Stress; Energy Metabolism; Fatty Liver; Glucose Intolerance; Hypoglycemic Agents; Insulin Resistance; Male; Mice, Inbred C57BL; Molecular Docking Simulation; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuroprotective Agents; Obesity; Palmitic Acid; Protein Binding; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Pyrazoles; Signal Transduction; Weight Gain

To investigate the protective effect and mechanism of curcumin derivatives B06 on myocardium from type 2 diabetic rats.. Thirty-five male SD rats were randomly divided into 5 groups, normal control group (NC group), high fat group (HF group), high fat treatment group (FT group), diabetes mellitus group (DM group) and diabetes treatment group (DT group) (n = 7). The late four groups were fed with high fat food, after four weeks of high fat feeding, the rats from DM group and DT group were injected with low dosage of streptozocin intraperitoneally to induce diabetes mellitus, FT group and DT group were gavaged with curcumin derivatives B06 at the dosage of 0.2 mg/kg x d. The blood glucose and lipid were detected biochemically, blood insulin was assayed by ELISA and the insulin resistance index was calculated, the morphology of myocardium was observed by light and transmission electron microscopy, the protein expression of AMP-activated protein kinase alpha (AMPKalpha) and phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) in myocardium were tested by Western blot.. The level of blood glucose, lipid, insulin and the insulin resistance index were increased in HF group and DM group, but they were decreased after the treatment with B06. The expression of AMPKalpha and p-AMPKalpha were decreased, but they became increased after the treatment of B06. There were increased collagen fibers in interstitium and expansion of mitochondria in cytoplasm of myocardium from DM group, but they were ameliorated in B06 treatment group.. It is suggested that B06 may relieve the damage of myocardium from type 2 diabetic rats and the increased expression of AMPKalpha and p-AMPKalpha may be involved in it.

Topics: AMP-Activated Protein Kinases; Animals; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Heart; Insulin Resistance; Male; Myocardium; Rats; Rats, Sprague-Dawley; Streptozocin

It was reported that increased plasma levels of free fatty acids (FFAs) are associated with profound insulin resistance in skeletal muscle and may also play a critical role in the insulin resistance of obesity and type 2 diabetes mellitus. Skeletal muscle is the major site for insulin-stimulated glucose uptake and is involved in energy regulation and homeostasis. In this study, we used 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC) activator, and palmitate to induce insulin resistance in C2C12 mouse skeletal muscle cells. Our data show that epigallocatechin gallate (EGCG) and curcumin treatment reduce insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, and curcumin is more potent to increase Akt phosphorylation in TPA induction. Moreover, we found that after 5 h of palmitate incubation, epicatechin gallate (ECG) can suppress IRS-1 Ser307 phosphorylation and significantly promote Akt, ERK1/2, p38 MAPK, and AMP-activated protein kinase activation. With a longer incubation with palmitate, IRS-1 exhibited a dramatic depletion, and treatment with EGCG, ECG, and curcumin could reverse IRS-1 expression, Akt phosphorylation, and MAPK signaling cascade activation and improve glucose uptake in C2C12 skeletal muscle cells, especially ECG and curcumin. In addition, treatment with these polyphenols can suppress acetyl-CoA carboxylase activation, but only EGCG could inhibit lipid accumulation in the intracellular site. These findings may suggest that curcumin shows the best capacity to improve FFA-induced insulin resistance than the other two, and ECG was more effective than EGCG in attenuating insulin resistance.

Topics: Animals; Catechin; Cell Line; Curcumin; Enzyme Activation; Fatty Acids, Nonesterified; Insulin Receptor Substrate Proteins; Insulin Resistance; Mice; Muscle, Skeletal; Palmitic Acid; Phosphorylation; Polyphenols; Protein Kinase C; Serine; Signal Transduction; Tetradecanoylphorbol Acetate

Mechanisms underlying the attenuation of body weight gain and insulin resistance in response to high fat diet (HFD) by the curry compound curcumin need to be further explored. Although the attenuation of the inflammatory pathway is an accepted mechanism, a recent study suggested that curcumin stimulates Wnt signaling pathway and hence suppresses adipogenic differentiation. This is in contrast with the known repressive effect of curcumin on Wnt signaling in other cell lineages.. We conducted the examination on low fat diet, or HFD fed C57BL/6J mice with or without curcumin intervention for 28 weeks. Curcumin significantly attenuated the effect of HFD on glucose disposal, body weight/fat gain, as well as the development of insulin resistance. No stimulatory effect on Wnt activation was observed in the mature fat tissue. In addition, curcumin did not stimulate Wnt signaling in vitro in primary rat adipocytes. Furthermore, curcumin inhibited lipogenic gene expression in the liver and blocked the effects of HFD on macrophage infiltration and the inflammatory pathway in the adipose tissue.. We conclude that the beneficial effect of curcumin during HFD consumption is mediated by attenuating lipogenic gene expression in the liver and the inflammatory response in the adipose tissue, in the absence of stimulation of Wnt signaling in mature adipocytes.

Topics: Adipocytes; Adipose Tissue; Adiposity; Animals; Curcumin; Dietary Fats; Dietary Supplements; Gene Expression Regulation; Glucose; Hep G2 Cells; Humans; Inflammation; Insulin; Insulin Resistance; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Time Factors; Weight Gain

Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes.. Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation.. Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05).. This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Carrier Proteins; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Fatty Acids, Nonesterified; Glycerol; Insulin Resistance; Isoproterenol; Lipase; Lipolysis; Mice; Obesity; Perilipin-1; Phosphoproteins; Phosphorylation; Phytotherapy; Plant Extracts; Tumor Necrosis Factor-alpha

Curcuma comosa Roxb. (C. comosa) is an indigenous medicinal herb that has been used in Thailand as a dietary supplement to relieve postmenopausal symptoms. Recently, a novel phytoestrogen, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol or compound 049, has been isolated and no study thus far has investigated the role of C. comosa in preventing metabolic alterations occurring in estrogen-deprived state. The present study investigated the long-term effects (12 weeks) of C. comosa hexane extract and compound 049 on insulin resistance in prolonged estrogen-deprived rats.. Female Sprague-Dawley rats were ovariectomized (OVX) and treated with C. comosa hexane extract (125 mg, 250 mg, or 500 mg/kg body weight (BW)) and compound 049 (50 mg/kg BW) intraperitoneally three times per week for 12 weeks. Body weight, food intake, visceral fat weight, uterine weight, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity, and GLUT-4 protein expression were determined.. Prolonged ovariectomy resulted in dyslipidemia, impaired glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as compared to SHAM. Treatment with C. comosa hexane extract and compound 049, three times per week for 12 weeks, markedly reduced serum total cholesterol and low-density lipoprotein levels, improved insulin sensitivity and partially restored uterine weights in ovariectomized rats. In addition, compound 049 or high doses of C. comosa hexane extract enhanced insulin-mediated glucose uptake in skeletal muscle and increased muscle GLUT-4 protein levels.. Treatment with C. comosa and its diarylheptanoid derivative improved glucose and lipid metabolism in estrogen-deprived rats, supporting the traditional use of this natural phytoestrogen as a strategy for relieving insulin resistance and its related metabolic defects in postmenopausal women.

Topics: Animals; Biological Transport; Cholesterol; Cholesterol, LDL; Curcuma; Diarylheptanoids; Dyslipidemias; Estrogens; Female; Glucose; Glucose Intolerance; Glucose Transporter Type 4; Heptanol; Insulin; Insulin Resistance; Muscle, Skeletal; Organ Size; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Uterus

Curcumin has been reported to lower plasma lipids and glucose in diabetic rats, and to decrease body weight in obese rats, which may partly be due to increased fatty acid oxidation and utilization in skeletal muscle.. Diabetic rats induced by high-fat diet plus streptozotocin (STZ, 30 mg/kg BW) were fed a diet containing 50, 150, or 250 mg/kg BW curcumin for 7 wk. Curcumin dose-dependently decreased plasma lipids and glucose and the dose 150 mg/kg BW appeared to be adequate to produce a significant effect. Curcumin supplementation reduced glucose and insulin tolerance measured as areas under the curve. L6 myotubes were treated with palmitate (0.25 mmol/L) in the presence of different levels of curcumin for 24 h in our in vitro experiment. Curcumin at 10 μmol/L was adequate to cause a significant increase in 2-deoxy-[(3)H]d-glucose uptake by L6 myotubes. Curcumin up-regulated expression of phosphorylated AMP-activated protein kinase (AMPK), CD36, and carnitine palmitoyl transferase 1, but down-regulated expression of pyruvate dehydrogenase 4 and phosphorylated glycogen synthase (GS) in both in vivo and in vitro studies. Moreover, curcumin increased phosphorylated acetyl COA carboxylase in L6 myotubes. The effects of curcumin on these enzymes except for GS were suppressed by AMPK inhibitor, Compound C. LKB1, an upstream kinase of AMPK, was activated by curcumin and inhibited by radicicol, an LKB1 destabilizer.. Curcumin improves muscular insulin resistance by increasing oxidation of fatty acid and glucose, which is, at least in part, mediated through LKB1-AMPK pathway.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Biological Transport; Cell Line; Curcumin; Deoxyglucose; Diabetes Mellitus, Experimental; Dietary Fats; Dietary Supplements; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Male; Muscle, Skeletal; Palmitic Acid; Protein Kinase Inhibitors; Protein Kinases; Protein Serine-Threonine Kinases; Random Allocation; Rats; Rats, Wistar; Signal Transduction

This study was conducted to investigate the effect of curcumin, obtained from Curcuma longa, in comparison with rosiglitazone on the progression of insulin resistance and type 2 diabetes mellitus (T2DM) and the mechanisms underlying this effect. Insulin resistance and T2DM was induced in male Sprague Dawley rats by high fat diet (HFD) feeding for 60 and for 75 days representing two regimens of the study, protection and treatment. Prophylactic oral administration of curcumin (80 mg/kg), rosiglitazone (1 mg/kg), their combination, or vehicle (in control groups) was started along with HFD feeding in different groups. Treatment is achieved by oral administration of the previously mentioned agents in the last 15 days of HFD feeding after induction of insulin resistance and T2DM in rats. Curcumin showed an anti-hyperglycemic effect and improved insulin sensitivity, and this action may be attributed at least in part to its anti-inflammatory properties as evident by attenuating TNF-α levels in HFD fed rats, and its anti-lipolytic effect as evident by attenuating plasma free fatty acids. The curcumin effects are comparable to those of rosiglitazone, which indicate that they may act similarly. Finally we can say that, curcumin could be a beneficial adjuvant therapy in patients with T2DM.

Topics: Administration, Oral; Analysis of Variance; Animals; Blood Glucose; Body Composition; Curcumin; Diabetes Mellitus, Type 2; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Rats; Rats, Sprague-Dawley; Rosiglitazone; Thiazolidinediones; Triglycerides; Tumor Necrosis Factor-alpha

To determine whether and by what mechanism systemic delivery of curcumin-containing liposomes improves insulin resistance in the leptin deficient (ob/ob) mouse model of insulin resistance.. Insulin resistant ob/ob mice with steatosis were injected intraperitoneally with liposome nanoparticles, entrapping the nuclear factor-κB (NF-κB) inhibitor curcumin (curcusomes), and uptake in liver and adipose tissue was determined by flow cytometry. The effects of curcusomes on macrophage NF-κB activation and cytokine production were assessed. Transfer experiments determined the role of hepatic tumor necrosis factor (TNF)/inducible nitric oxide synthase-producing dendritic cells (Tip-DCs) and adipose tissue macrophages (ATMs) in inflammation-induced insulin resistance, determined by homeostatic assessment of insulin resistance.. Phagocytic myeloid cells infiltrating the liver in ob/ob mice had the phenotypic characteristics of Tip-DCs that arise from monocyte precursors in the liver and spleen after infection. Targeting Tip-DCs and ATMs with curcusomes in ob/ob mice reduced NF-κB/RelA DNA binding activity, reduced TNF, and enhanced interleukin-4 production. Curcusomes improved peripheral insulin resistance.. Both hepatic Tip-DCs and ATMs contribute to insulin resistance in ob/ob mice. Curcusome nanoparticles inhibit proinflammatory pathways in hepatic Tip-DCs and ATMs and reverse insulin resistance. Targeting inflammatory DCs is a novel approach for type 2 diabetes treatment.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Dendritic Cells; Drug Delivery Systems; Gene Expression Regulation; Insulin Resistance; Leptin; Liposomes; Liver; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Nanoparticles; NF-kappa B; Obesity; RNA, Messenger; Specific Pathogen-Free Organisms; Tissue Distribution

High consumption of dietary fructose is an important contributory factor in the development of hepatic steatosis in insulin or leptin resistance. We investigated the effects of curcumin on fructose-induced hypertriglyceridemia and liver steatosis and explored its preventive mechanisms in rats. Curcumin reduced serum insulin and leptin levels in fructose-fed rats. This compound could increase phosphorylation of insulin receptor and insulin receptor substrate 1 to enhance Akt and extracellular signal-regulated kinase1/2 (ERK1/2) activation in the liver of fructose-fed rats. Moreover, curcumin increased phosphorylation of hepatic janus-activated kinase-signal transducer 2 and subsequently also stimulated Akt and ERK1/2 activation in this model. Suppression of curcumin on leptin signaling overstimulation in tyrosine1138 phosphorylation of the long form of leptin receptor and signal transducer and activator of transcription 3 resulted in down-regulation of suppressor of cytokine signaling 3 in the liver of fructose-fed rats. Thus, improvement of insulin and leptin signaling transduction and subsequently elevation of peroxisome proliferator-activated receptor alpha expression by curcumin led to reduction of very-low-density lipoprotein overproduction and triglyceride hypersynthesis. Furthermore, overexpression and hyperactivity of hepatic protein tyrosine phosphatase 1B (PTP1B) associated with defective insulin and leptin signaling were observed in fructose-fed rats. Additionally, curcumin was found to significantly reduce hepatic PTP1B expression and activity in this model.. Our data indicate that the mechanisms by which curcumin protects against fructose-induced hypertriglyceridemia and hepatic steatosis are its inhibition on PTP1B and subsequently improvement of insulin and leptin sensitivity in the liver of rats. This PTP1B inhibitory property may be a promising therapeutic strategy for curcumin to treat fructose-induced hepatic steatosis driven by hepatic insulin and leptin resistance.

Topics: Animals; Curcumin; Dietary Carbohydrates; Extracellular Signal-Regulated MAP Kinases; Fatty Liver; Fructose; Hypertriglyceridemia; Insulin Resistance; Leptin; Liver; Male; Pioglitazone; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Thiazolidinediones

Adiponectin is positively correlated with insulin sensitivity. Hydroxycinnamic acid derivatives (HADs), observed ubiquitously in plants, have some physiological functions. In this study, we investigated the effect of HADs on serum adiponectin concentrations in mice and on adiponectin secretion of 3T3-L1 adipocytes. In mice, serum adiponectin concentrations were increased by gamma-oryzanol administration. CAPE, curcumin, and trans-ferulic acid markedly enhanced the adiponectin secretion of 3T3-L1 adipocytes, but not gamma-oryzanol. To clarify the effects of gamma-oryzanol in mice or the effects of HADs on the underlying mechanisms of adiponectin secretion, we further investigated the effect of HADs on adiponectin secretion in the NF-kappaB activation state. Although the adiponectin secretion was reduced in the presence of lipopolysaccharide plus TNF-alpha and IFN-gamma, only gamma-oryzanol supported the activity of adiponectin secretion under NF-kappaB activated condition. The results indicate that these HADs might regulate adiponectin secretion by the inhibition of NF-kappaB activation. HADs might be effective for ameliorating type 2 diabetes.

Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Animals; Caffeic Acids; Coumaric Acids; Curcumin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Interferon-gamma; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Phenylethyl Alcohol; Phenylpropionates; Phytotherapy; Pioglitazone; Plant Extracts; Plant Oils; Rice Bran Oil; Thiazolidinediones; Tumor Necrosis Factor-alpha

To investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric (Curcuma longa) on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes.. Glucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 (NF-kappa p65) and mitogen-activated protein kinase (MAPKs) were detected by Western blot assay.. The basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-alpha and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kappaB. The activities of Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase1/2 (ERK1/2) and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 (inhibitor of JNK) instead of PD98059 or SB203580 (inhibitor of ERK1/2 or p38MAPK, respectively) decreased the up-regulation of TNF-alpha induced by palmitate.. Curcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kappaB and JNK pathway.

Topics: 3T3-L1 Cells; Animals; Anthracenes; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Glucose; Insulin; Insulin Resistance; Interleukin-6; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Mice; NF-kappa B; Palmitates; Protein Kinase Inhibitors; Tumor Necrosis Factor-alpha; Up-Regulation

This study investigated the effect of curcumin (0.05-g/100-g diet) supplementation on a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) fed to hamsters, one of the rodent species that are most closely related to humans in lipid metabolism. Curcumin significantly lowered the levels of free fatty acid, total cholesterol, triglyceride, and leptin and the homeostasis model assessment of insulin resistance index, whereas it elevated the levels of high-density lipoprotein cholesterol and apolipoprotein (apo) A-I and paraoxonase activity in plasma, compared with the control group. The levels of hepatic cholesterol and triglyceride were also lower in the curcumin group than in the control group. In the liver, fatty acid beta-oxidation activity was significantly higher in the curcumin group than in the control group, whereas fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and acyl coenzyme A:cholesterol acyltransferase activities were significantly lower. Curcumin significantly lowered the lipid peroxide levels in the erythrocyte and liver compared with the control group. These results indicate that curcumin exhibits an obvious hypolipidemic effect by increasing plasma paraoxonase activity, ratios of high-density lipoprotein cholesterol to total cholesterol and of apo A-I to apo B, and hepatic fatty acid oxidation activity with simultaneous inhibition of hepatic fatty acid and cholesterol biosynthesis in high-fat-fed hamsters.

Topics: Animals; Apolipoprotein A-I; Aryldialkylphosphatase; Cardiovascular Diseases; Cholesterol, HDL; Cricetinae; Curcumin; Dietary Fats; Fatty Acids; Hyperlipidemias; Hypolipidemic Agents; Insulin Resistance; Leptin; Lipid Peroxidation; Male; Mesocricetus

To evaluate the insulin and leptin resistance of curcumin on simplicity obesity rats.. All 50 SPF grade healthy Sprague-Dawley male initial weaning rats were used for two groups in stratified sampling by weight: 30 in treated group and 20 in control group. They were assigned to the following treatment for 8 weeks: the treated group was fed with high-fat food and the control group was fed with normal food. Eight weeks later, adiposity model rats were prepared. Groups: adiposity model rats were divided into 3 groups: model + low curcumin (1.25 g/kg), model + high curcumin (5.00 g/kg) and a model group. In addition, there also had a normal control and a control + high curcumin (5.00 g/kg) group. Ten rats in every group and all given ground feed. After intragastric administration in different doses of curcumin 4 weeks, the effects and pathological changes were observed by the blood sugar, insulin, leptin and TNF-alpha, pathology and transmission electron microscope of pancreatic gland.. Given 4 weeks the different dose of curcumin on the simplicity obesity rats, the significant diminished weight (435.0 +/- 37.6) g and content of lipocyte (4.78 +/- 1.87) g as compared with the obesity model control (492.3 +/- 14.8) g and (8.94 +/- 1.88) g (t values were 4.484 and 4.961 respectively, P < 0.01), level of blood sugar (4.50 +/- 0.09) mmol/L, insulin (7.43 +/- 0.65) mmol/L, leptin (3.40 +/- 0.39) mmol/L and TNF-alpha (2.42 +/- 0.19) ng/ml were significantly decreased than those of adiposity model rats (4.94 +/- 0.12) mmol/L, (9.30 +/- 0.21) mmol/L, (4.40 +/- 0.23) mmol/L and (2.86 +/- 0.49) ng/ml (t values were 8.297, 7.743, 6.247 and 2.368 respectively, P < 0.05), and there was no significant difference with the control group (4.30 +/- 0.14) mmol/L on the level of blood sugar (t = 0.399, P > 0.05). There were a lot of secretory granules with large sphere volume in beta cells of pancreatic island found by transmission electron microscope, and these secretory granules had a higher electron density than those in non-disposed groups.. By diminishing the sediment of fat, relaxing the lymphatic return, and refraining the apoptosis of beta cells, the curcumin might significantly decrease the level of insulin resistance and leptin resistance caused by the high fat diet.

Topics: Animals; Apoptosis; Curcumin; Disease Models, Animal; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.

Topics: Adipose Tissue; Animals; Blood Glucose; Curcumin; Diabetes Mellitus; Dietary Supplements; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Insulin; Insulin Resistance; Lipoprotein Lipase; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Muscle, Skeletal