peptide-yy and Insulin-Resistance

Considering conflicting results on the consequences of all types of obesity surgery, we were to summarize them via a systematic review.. Electronic literature search was done via scientific search engines. After the removal of duplicates and selection of articles of interest, 771 studies were included.. Insulin resistance indicators were significantly improved after bariatric surgery. Leptin was also significantly decreased while adiponectin was significantly increased. Although the level of metabolic hormones changed after bariatric surgery, they were not statistically significant. Inflammation indicators were significantly decreased. Significant reduction was also detected in PAI-1 and sICAM-1.. Bariatric surgery is beneficial in morbidly obese patients. Although treating obesity in a surgical way may cause some complications, the weight loss is generally safe and effective.

Topics: Adiponectin; Bariatric Surgery; C-Reactive Protein; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Obesity, Morbid; Peptide YY; Plasminogen Activator Inhibitor 1; Tumor Necrosis Factor-alpha

Bariatric surgery has emerged as the most durably effective treatment of type 2 diabetes (DM). However, the mechanisms governing improvement in glucose homeostasis have yet to be fully elucidated. In this review we discuss the various types of surgical interventions and the multitude of factors that potentially mediate the effects on glycemia, such as altered delivery of nutrients to the distal ileum, duodenal exclusion, gut hormone changes, bile acid reabsorption, and amino acid metabolism. Accumulating evidence that some of these changes seem to be independent of weight loss questions the rationale of using body mass index as the major indication for surgery in diabetic patients. Understanding the complex mechanisms and interactions underlying improved glycemic control could lead to novel therapeutic targets and would also allow for greater individualization of therapy and optimization of surgical outcomes.

Topics: Bariatric Surgery; Body Mass Index; Caloric Restriction; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucose; Glycated Hemoglobin; Homeostasis; Humans; Incretins; Insulin Resistance; Male; Obesity, Morbid; Peptide YY; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Weight Loss

Polycystic ovary syndrome (PCOS) is an endocrine disease of women in reproductive age. It is characterized by anovulation and hyperandrogenism. Most often patients with PCOS have metabolic abnormalities such as dyslipidemia, insulin resistance, and glucose intolerance. It is not surprising that obesity is high prevalent in PCOS. Over 60 % of PCOS women are obese or overweight. Modulation of appetite and energy intake is essential to maintain energy balance and body weight. The gastrointestinal tract, where nutrients are digested and absorbed, plays a central role in energy homeostasis. The signals from the gastrointestinal tract arise from the stomach (ghrelin release), proximal small intestine (CCK release), and distal small intestine (GLP-1 and PYY) in response to food. These hormones are recognized as "appetite regulatory hormones." Weight loss is the key in the treatments of obese/overweight patients with PCOS. However, current non-pharmacologic management of body weight is hard to achieve. This review highlighted the gastrointestinal hormones, and discussed the potential strategies aimed at modifying hormones for treatment in PCOS.

Topics: Cholecystokinin; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Peptide YY; Polycystic Ovary Syndrome

Bariatric surgery managing/preventing complications of severe overweight is nowadays widely accepted as a mainstay in the treatment of morbid obesity. Its role is particularly important in type 2 diabetes developing on the base of long-standing significant overweight. The glycemic control improves within days-weeks after these surgeries, when weight loss and reduction of the visceral fat mass is barely detectable. This short term effect is probably due to an increased secretion of glucagon-like peptide and, as a consequence, an improvement in hepatic insulin sensitivity as well as the whole body glucose uptake. Besides the prolonged glucagon-like peptide effects, the favourable long term effect of these operations - lasting for 10 years even after surgery - is the decrease of visceral fat mass and elimination of harmful influence of cytokines produced by the fatty tissue. The article overviews the metabolic effects of these procedures, their undoubted advantages and potential risks.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Hungary; Insulin; Insulin Resistance; Intra-Abdominal Fat; Male; Obesity, Morbid; Peptide YY; United States; Weight Loss

The intestine is an important metabolic organ that has gained attention in recent years for the newly identified role that it plays in the pathophysiology of various metabolic diseases including obesity, insulin resistance and diabetes. Recent insights regarding the role of enteroendocrine hormones, such as GIP, GLP-1, and PYY in metabolic diseases, as well as the emerging role of the gut microbial community and gastric bypass bariatric surgeries in modulating metabolic function and dysfunction have sparked a wave of interest in understanding the mechanisms involved, in an effort to identify new therapeutics and novel regulators of metabolism. This review summarizes the current evidence that the gastrointestinal tract has a key role in the development of obesity, inflammation, insulin resistance and diabetes and discusses the possible players that can be targeted for therapeutic intervention.

Topics: Animals; Bariatric Surgery; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Gastrointestinal Tract; Glucagon-Like Peptide 1; Humans; Inflammation; Insulin Resistance; Metabolic Diseases; Metagenome; Obesity; Peptide YY

The gut-derived hormone peptide YY (PYY) is most commonly known for its effect on satiety, decreasing food intake and body weight in animals and humans. However, PYY is also involved in a wide range of digestive functions including regulating insulin secretion and glucose homeostasis. Over the last few years, there have been several interesting clinical and animal studies investigating the role of PYY in glucose homeostasis. This review aims to present an updated summary of findings over the last few decades highlighting the role of PYY in regulating insulin output and insulin sensitivity, and the potential mechanisms involved.

Topics: Animals; Clinical Trials as Topic; Glucose; Homeostasis; Humans; Insulin Resistance; Peptide YY

Topics: Abnormalities, Multiple; Child; Drug Resistance; Endocrine System Diseases; Energy Metabolism; Ghrelin; Homeostasis; Hormones; Humans; Hypothalamus, Middle; Insulin; Insulin Resistance; Leptin; Obesity; Peptide Fragments; Peptide Hormones; Peptide YY; Sympathetic Nervous System; Vagus Nerve

Evidence is emerging that interdaily meal pattern variability potentially affects response such as thermic effect of food (TEF), macronutrient metabolism, and appetite.. To investigate the effect of irregular meal pattern on TEF, glucose, insulin, lipid profile, and appetite regulation in women who are overweight or with obesity and confirmed insulin resistance.. In a randomized crossover trial, 9 women [mean ± SD BMI (in kg/m2): 33.3 ± 3.1] with confirmed insulin resistance consumed a regular (14 d; 6 meals/d) and an irregular (14 d; 3-9 meals/d) meal pattern separated by a 14-d washout interval. Identical foods were provided during the interventions, and at the start and end of each meal pattern, participants attended the laboratory after an overnight fast. Energy expenditure, glucose, insulin, lipids, adiponectin, leptin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin were measured at baseline and for 3 h after consumption of a test drink, after which an ad libitum test meal was offered. Subjective appetite ratings were recorded before and after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 7 consecutive days during each intervention.. TEF (over 3 h) was significantly lower postirregular intervention compared with postregular (97.7 ± 19.2 kJ*3 h in postregular visit and 76.7 ± 35.2 kJ*3 h in postirregular visit, paired t test, P = 0.048). Differences in HOMA-IR between the 2 interventions (3.3 ± 1.7 and 3.6 ± 1.6 in postregular and postirregular meal pattern, respectively) were not significant. Net incremental AUC for GLP-1 concentrations (over 3 h) for the postregular meal pattern were higher (864.9 ± 456.1 pmol/L*3 h) than the postirregular meal pattern (487.6 ± 271.7 pmol/L*3 h, paired t test, P = 0.005).. Following a 14-d period of an irregular meal pattern, TEF was significantly less than following a regular meal pattern, potentially compromising weight management if sustained long term. This study was registered at www.clinicaltrials.gov as NCT02582606.

Topics: Adiponectin; Adolescent; Adult; Appetite; Blood Glucose; Blood Glucose Self-Monitoring; Energy Metabolism; Feeding Behavior; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Meals; Middle Aged; Obesity; Overweight; Peptide YY; Thermogenesis; Young Adult

Fructose compared to glucose has adverse effects on metabolic function, but endocrine responses to oral sucrose vs glucose is not well understood.. We investigated how oral sucrose vs glucose affected appetite-regulating hormones, and how biological factors (body mass index [BMI], insulin sensitivity, sex) influence endocrine responses to these 2 types of sugar.. Sixty-nine adults (29 men; 23.22 ± 3.74 years; BMI 27.03 ± 4.96 kg/m2) completed the study. On 2 occasions, participants consumed 300-mL drinks containing 75 g of glucose or sucrose. Blood was sampled at baseline, 10, 35, and 120 minutes post drink for plasma glucose, insulin, glucagon-like peptide (GLP-1)(7-36), peptide YY (PYY)total, and acyl-ghrelin measures. Hormone levels were compared between conditions using a linear mixed model. Interaction models were performed, and results were stratified to assess how biological factors influence endocrine responses.. Sucrose vs glucose ingestion provoked a less robust rise in glucose (P < .001), insulin (P < .001), GLP-1 (P < .001), and PYY (P = .02), whereas acyl-ghrelin suppression was similar between the sugars. We found BMI status by sugar interactions for glucose (P = .01) and PYY (P = .03); obese individuals had smaller increases in glucose and PYY levels after consuming sucrose vs glucose. There were interactions between insulin sensitivity and sugar for glucose (P = .003) and insulin (P = .04), and a sex by sugar interaction for GLP-1 (P = .01); men demonstrated smaller increases in GLP-1 in response to oral sucrose vs glucose.. Sucrose is less efficient at signaling postprandial satiation than glucose, and biological factors influence differential hormone responses to sucrose vs glucose consumption.

Topics: Administration, Oral; Adolescent; Adult; Appetite; Appetite Regulation; Blood Glucose; Body Mass Index; Down-Regulation; Eating; Female; Ghrelin; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Obesity; Peptide YY; Satiation; Sex Characteristics; South Carolina; Sucrose; Young Adult

It has been shown recently that metabolic syndrome is associated with gut dysbiosis. The gut microbiota may be the main target for prevention or treatment of metabolic syndrome. We investigated the effects of synbiotic supplementation on metabolic syndrome. In this triple-blinded clinical trial, 46 Iranian patients with metabolic syndrome, from both sexes, aged 25-70 years, who fulfilled inclusion criteria were randomly categorized to receive either the synbiotic or a placebo capsule, twice a day for three months, plus a weight-loss diet using stratified random sampling based on body mass index (BMI). Each synbiotic capsule consisted of seven strains probiotic bacteria (2× 10

Topics: Adult; Aged; Appetite; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Fasting; Female; Humans; Inflammation Mediators; Insulin; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Middle Aged; Peptide YY; Research Design; Synbiotics; Treatment Outcome

To assess the effects of walnuts on cardiometabolic outcomes in obese people and to explore the underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic and microbiome analysis, integrated with lipid particle fractionation, appetite-regulating hormones and haemodynamic measurements.. A total of 10 obese individuals were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. The participants had two 5-day inpatient stays, during which they consumed a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts, with a 1-month washout period between the two visits.. Walnut consumption improved aspects of the lipid profile; it reduced fasting small and dense LDL particles (P < 0.02) and increased postprandial large HDL particles (P < 0.01). Lipoprotein insulin resistance score, glucose and the insulin area under the curve (AUC) decreased significantly after walnut consumption (P < 0.01, P < 0.02 and P < 0.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with eight of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. The peptide YY AUC significantly increased after walnut consumption (P < 0.03). No major significant changes in haemodynamic or metabolomic analysis or in microbiome host health-promoting bacteria such as Faecalibacterium were found.. These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic variables. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption, which may explain the longer-term benefits of walnuts or other nuts on insulin resistance, cardiovascular risk and mortality.

Topics: Cardiovascular Diseases; Cross-Over Studies; Diet; Double-Blind Method; Eating; Fasting; Female; Humans; Inpatients; Insulin Resistance; Juglans; Lipids; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Protective Factors

It is known that the macronutrient content of a meal has different impacts on the postprandial satiety and appetite hormonal responses. Whether obesity interacts with such nutrient-dependent responses is not well characterized. We examined the postprandial appetite and satiety hormonal responses after a high-protein (HP), high-carbohydrate (HC), or high-fat (HF) mixed meal. This was a randomized cross-over study of 9 lean insulin-sensitive (mean±SEM HOMA-IR 0.83±0.10) and 9 obese insulin-resistant (HOMA-IR 4.34±0.41) young (age 21-40 years), normoglycaemic Chinese men. We measured fasting and postprandial plasma concentration of glucose, insulin, active glucagon-like peptide-1 (GLP-1), total peptide-YY (PYY), and acyl-ghrelin in response to HP, HF, or HC meals. Overall postprandial plasma insulin response was more robust in the lean compared to obese subjects. The postprandial GLP-1 response after HF or HP meal was higher than HC meal in both lean and obese subjects. In obese subjects, HF meal induced higher response in postprandial PYY compared to HC meal. HP and HF meals also suppressed ghrelin greater compared to HC meal in the obese than lean subjects. In conclusion, a high-protein or high-fat meal induces a more favorable postprandial satiety and appetite hormonal response than a high-carbohydrate meal in obese insulin-resistant subjects.

Topics: Adult; Asian People; Blood Glucose; Cross-Over Studies; Diet, High-Fat; Diet, High-Protein; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Obesity; Peptide YY; Postprandial Period; Satiety Response; Singapore; Young Adult

Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved.. In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses.. Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p<0.001). The postprandial responses of GIHs and appetite hormones were similar after both diet regimens.. Both hypocaloric diet regimens reduced fasting leptin and GIP and postprandial response of GIP comparably. The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Eating only breakfast and lunch increased fasting plasma ghrelin more than the same caloric restriction split into six meals. The changes in fasting ghrelin correlated negatively with the decrease in body weight. These results suggest that for type 2 diabetic patients on a hypocaloric diet, eating larger breakfast and lunch may be more efficient than six smaller meals during the day.

Topics: Adult; Aged; Body Weight; Caloric Restriction; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Insulin Resistance; Leptin; Male; Meals; Middle Aged; Pancreatic Polypeptide; Peptide YY; Time Factors; Treatment Outcome

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.

Topics: Adult; Appetite Regulation; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Enteroendocrine Cells; Feeding Behavior; Female; Gastrectomy; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Italy; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Time Factors; Weight Loss

High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption.. Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate.. At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories).. Consuming 30 g HAM-RS2 daily for 6 weeks can improve glucose homeostasis, lower leptin concentrations, and increase fasting PYY in healthy overweight adults without impacting body composition and may aid in the prevention of chronic disease. However, between-group differences in biomarkers were not observed and future research is warranted before specific recommendations can be made.. None.

Topics: Absorptiometry, Photon; Adiposity; Adolescent; Adult; Biomarkers; Blood Glucose; Diet, High-Fat; Double-Blind Method; Female; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Overweight; Peptide YY; Postprandial Period; Satiation; Starch; Young Adult; Zea mays

Activation of free fatty acid receptor (FFAR)2 and FFAR3 via colonic short-chain fatty acids, particularly propionate, are postulated to explain observed inverse associations between dietary fiber intake and body weight. Propionate is reported as the predominant colonic fermentation product from l-rhamnose, a natural monosaccharide that resists digestion and absorption reaching the colon intact, while effects of long-chain inulin on appetite have not been extensively investigated. In this single-blind randomized crossover study, healthy unrestrained eaters (n = 13) ingested 25.5 g/d l-rhamnose, 22.4 g/d inulin or no supplement (control) alongside a standardized breakfast and lunch, following a 6-d run-in to investigate if appetite was inhibited. Postprandial qualitative appetite, breath hydrogen, and plasma glucose, insulin, triglycerides and non-esterified fatty acids were assessed for 420 min, then an ad libitum meal was provided. Significant treatment x time effects were found for postprandial insulin (P = 0.009) and non-esterified fatty acids (P = 0.046) with a significantly lower insulin response for l-rhamnose (P = 0.023) than control. No differences between treatments were found for quantitative and qualitative appetite measures, although significant treatment x time effects for meal desire (P = 0.008) and desire to eat sweet (P = 0.036) were found. Breath hydrogen was significantly higher with inulin (P = 0.001) and l-rhamnose (P = 0.009) than control, indicating colonic fermentation. These findings suggest l-rhamnose may inhibit postprandial insulin secretion, however neither l-rhamnose or inulin influenced appetite.

Topics: Adolescent; Adult; Appetite; Blood Glucose; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Colon; Cross-Over Studies; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Dietary Supplements; Energy Intake; Fatty Acids, Nonesterified; Female; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Insulin Secretion; Inulin; Male; Middle Aged; Peptide YY; Postprandial Period; Propionates; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Rhamnose; Single-Blind Method; Waist Circumference; Young Adult

Administration of ghrelin inhibits the acute insulin response to glucose and worsens IV glucose tolerance in healthy subjects. Evidence from preclinical studies suggests that ghrelin may have differential effects on glucose metabolism during fasting and feeding. Our objective was to test the effects of ghrelin on glucose and insulin responses during a meal tolerance test.. Acyl ghrelin (0.26 and 2.0 μg/kg/h) or saline was infused in 13 healthy subjects on three separate occasions in randomized order. Ghrelin was infused for 45 minutes to achieve steady-state levels and continued for 240 minutes after ingestion of a liquid test meal. Primary outcomes were area under the curve for glucose and insulin secretion.. We found that ghrelin infusions of 0.26 and 2.0 μg/kg/h raised steady-state plasma total ghrelin levels to 1.7- and 4.8-fold above fasting concentrations, but did not alter fasting plasma glucose or insulin levels. During the meal tolerance test, ghrelin decreased insulin sensitivity, impaired β-cell function, and induced glucose intolerance. The high-dose ghrelin infusion also raised postprandial glucagon like peptide 1 secretion without affecting glucose dependent insulinotropic polypeptide, glucagon, or peptide YY concentrations.. We conclude that both physiologic and pharmacologic doses of ghrelin worsen the glucose and β-cell responses to meal ingestion in healthy humans. The increase in postprandial glucagon like peptide 1 secretion by ghrelin suggests a novel enteroendocrine connection, but does not mitigate the glucose intolerance.

Topics: Adult; Blood Glucose; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Peptide YY; Postprandial Period; Young Adult

Gut hormones change with weight loss in adults but are not well studied in obese youth.. The primary aim was to evaluate how gut hormones and subjective appetite measure change with dietary weight loss in obese adolescents.. Participants were a subset of those taking part in the 'Eat Smart Study'. They were aged 10-17 years with body mass index (BMI) > 90th centile and were randomized to one of three groups: wait-listed control, structured reduced carbohydrate or structured low-fat dietary intervention for 12 weeks. Outcomes were fasting glucose, insulin, leptin, adiponectin, total amylin, acylated ghrelin, active glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP) and total peptide tyrosine-tyrosine. Pre- and postprandial subjective sensations of appetite were assessed using visual analogue scales.. Of 87 'Eat Smart' participants, 74 participated in this sub-study. The mean (standard deviation) BMI z-score was 2.1 (0.4) in the intervention groups at week 12 compared with 2.2 (0.4) in the control group. Fasting insulin (P = 0.05) and leptin (P = 0.03) levels decreased, while adiponectin levels increased (P = 0.05) in the intervention groups compared with control. The intervention groups were not significantly different from each other. A decrease in BMI z-score at week 12 was associated with decreased fasting insulin (P < 0.001), homeostatic model of assessment-insulin resistance (P < 0.001), leptin (P < 0.001), total amylin (P = 0.03), GIP (P = 0.01), PP (P = 0.02) and increased adiponectin (P < 0.001). There was no significant difference in appetite sensations.. Modest weight loss in obese adolescents leads to changes in some adipokines and gut hormones that may favour weight regain.

Topics: Adiponectin; Adolescent; Adult; Appetite; Body Mass Index; Body Weight; Fasting; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Male; Pediatric Obesity; Peptide YY; Postprandial Period; Weight Loss

Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity.. Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes.. Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose.. Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating.

Topics: Acylation; Adolescent; Double-Blind Method; Eating; Female; Fructose; Gastrointestinal Hormones; Ghrelin; Glucose; Humans; Hunger; Hyperphagia; Insulin; Insulin Resistance; Male; Pediatric Obesity; Peptide YY; Postprandial Period

There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

Topics: Adolescent; Adult; Blood Glucose; Cohort Studies; Cross-Over Studies; Diet, Paleolithic; Glucagon-Like Peptide 1; Humans; Incretins; Insulin; Insulin Resistance; Insulin Secretion; Male; Meals; Patient Compliance; Peptide YY; Postprandial Period; Satiety Response; Time Factors; Up-Regulation; Young Adult

Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H₂ excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome.

Topics: Aged; Appetite Regulation; Biomarkers; Bread; Breakfast; Cohort Studies; Colon; Cross-Over Studies; Elder Nutritional Physiological Phenomena; Female; Fermentation; Gastrointestinal Microbiome; Glucagon-Like Peptides; Hordeum; Humans; Inflammation Mediators; Insulin Resistance; Intestinal Mucosa; Male; Middle Aged; Peptide YY; Whole Grains

The present study investigated the postprandial glycemic and insulinemic responses, the levels of satiety-related proteins, and substrate use after a single dose of a meal replacement (MR) with a high soy protein content and a low glycemic index (GI). The results were compared with a standardized breakfast showing a high GI and a low protein content.. Eleven overweight or obese male subjects with the metabolic syndrome and insulin resistance were included in the study. In the morning, each subject consumed, in a randomized design, 65 g of a MR or an isocaloric standardized breakfast. Four hours after breakfast, all subjects consumed the same standardized lunch. Blood levels of glucose, insulin, ghrelin, protein YY(PYY), oxygen uptake, and carbon dioxide production were determined and the respiratory quotient and substrate use were calculated.. The glycemic and insulinemic responses were considerably higher after the standardized breakfast. In addition, in these obese insulin-resistant subjects, the postprandial decease in fat oxidation was significantly less pronounced after intake of the MR. This effect was also detectable after lunch in terms of a second meal effect. Ghrelin levels were significantly lower 2 h after the intake of the MR and PYY levels tended higher.. Compared with the high GI/low-protein SB, a high soy protein MR with a low GI was associated with lower glycemia and insulinemia and relatively higher fat oxidation in the postprandial period. Together with a favorable course of appetite-regulating hormones, this could further help to explain the beneficial role of MR regimines high in soy protein for weight reduction and improvement of metabolic risk factors.

Topics: Appetite Regulation; Body Mass Index; Diet, Reducing; Energy Intake; Food, Formulated; Ghrelin; Glycemic Index; Humans; Hyperglycemia; Hyperinsulinism; Insulin Resistance; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Oxygen Consumption; Peptide YY; Postprandial Period; Soybean Proteins

A variety of dietary fibers have been shown to alter satiety hormone gene expression and secretion. The objective of this study was to examine plasma satiety hormone concentrations in healthy subjects consuming either PolyGlycopleX (PGX) or control (skim milk powder) for 21 days.. A randomized, double-blind, placebo-controlled clinical study was conducted in 54 healthy male and female adults. Participants consumed 5 g per day of PGX or control for 1 week followed by 2 additional weeks of 10 g per day of assigned product (n=27 per group). Primary outcomes measured at three visits (V1, V2 and V3) were plasma active glucagon-like peptide-1 (GLP-1) total ghrelin, peptide YY (PYY) and insulin.. There was a significant effect of visit for fasting PYY with control participants experiencing decreased PYY levels over time while PGX prevented this decline. When stratified by body mass index (BMI), PGX increased fasting PYY levels from week 1 to week 3 compared with control in participants with BMI <23 kg/m(2). There was a significant effect of visit for fasting ghrelin with levels decreasing in both PGX and control groups over time. No differences were detected in fasting GLP-1 levels. Although there was a 14% reduction in fasting insulin between V1 and V3 with PGX this was not significantly different from control.. PGX is a highly viscous, functional fiber that modifies satiety hormone secretion in healthy adults. Its' potential to act similarly in overweight adults warrants investigation.

Topics: Adolescent; Adult; Alginates; Body Mass Index; Dietary Fiber; Dietary Supplements; Double-Blind Method; Drug Combinations; Female; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Overweight; Peptide YY; Polysaccharides, Bacterial; Time Factors; Young Adult

The objective of this study was to investigate the effect of long-term exercise training on concentrations of five hormones related to appetite and insulin resistance in overweight adolescents. In addition, we were interested in the relationships of these hormones with each other and with anthropometric and/or cardiovascular disease marker changes. Participants were >or=the 85th percentile for BMI for age and sex and participated in an 8-month supervised aerobic training program. Anthropometrics, cardiovascular fitness assessment, and fasting blood samples were taken pre- and post-training. Glucose, insulin, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, leptin, active ghrelin, total peptide YY (PYY), adiponectin, and resistin concentrations were measured. The participants increased their time to exhaustion on an incremental treadmill test and decreased both percent body fat and blood triglyceride concentrations. Total PYY concentration increased and resistin concentration decreased after long-term exercise training, which are favorable outcomes. Leptin concentrations were related to weight, percent body fat, waist circumference, and triglyceride concentrations pre- and post-training. The changes in resistin concentrations were related to the changes in triglyceride concentrations. We conclude that long-term exercise training has beneficial effects for overweight adolescents with respect to PYY and resistin, hormones related to appetite and insulin sensitivity.

Topics: Adiponectin; Adiposity; Adolescent; Appetite; Biomarkers; Blood Glucose; Cardiovascular Diseases; Exercise Therapy; Exercise Tolerance; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Overweight; Peptide YY; Resistin; Time Factors; Treatment Outcome; Triglycerides

Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (-8.3 +/- 1.1 vs. -2.8 +/- 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (DeltaI(0-30)/DeltaG(0-30)) and GIP (Delta(0-30)) secretion were correlated (r = 0.69, P = 0.05). The PYY(3-36) (Delta(0-30)) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

Topics: Aged; Blood Glucose; Body Mass Index; Diet, Reducing; Eating; Exercise; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Obesity; Peptide Fragments; Peptide YY; Physical Fitness; Satiety Response

Carbohydrate-restricted diets (CRDs) have been shown to reduce body weight, whereas whole egg intake has been associated with increased satiety. The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones. Using a randomized blind parallel design, subjects were allocated to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) group for 12 weeks while following a CRD. There were significant reductions in fasting insulin (P < .025) and fasting leptin concentrations (P < .01) for both groups, which were correlated with the reductions in body weight and body fat (P < .05 and P < .01, respectively). Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance (P < .025). There was a significant decrease in serum glucose levels observed after the intervention. We did not observe the expected increases in plasma ghrelin levels associated with weight loss, suggesting a mechanism by which subjects do not increase appetite with CRD. To confirm these results, the subjective measures of satiety using visual analog scale showed that both groups felt more "full" (P < .05), "satisfied" (P < .001), and "wanted to eat less" (P < .001) after the intervention. These results indicate that inclusion of eggs in the diet (additional dietary cholesterol) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones.

Topics: Adult; Aged; Analysis of Variance; Appetite; Blood Glucose; Body Composition; Body Weight; Cholesterol, Dietary; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Proteins; Eggs; Energy Intake; Ghrelin; Hormones; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Pancreatic Polypeptide; Peptide YY; Satiation

Ghrelin and peptide YY (PYY) are both hormones derived from the gastrointestinal tract involved in appetite regulation. The cholinergic part of the vagal nerve is involved in the regulation of glucose and insulin. The aim of this study was to examine the effects of the cholinergic antagonist atropine on ghrelin, PYY, glucose, and insulin under basal conditions and after meal ingestion in lean and obese subjects.. Eight lean and eight obese subjects were included in a randomized, double-blind, placebo-controlled crossover study with 4 study days in randomized order (atropine/placebo +/- breakfast). Plasma ghrelin, PYY, insulin, and glucose were measured. Hunger and satiety feelings were rated on a 10-cm visual analog scale.. In lean individuals, atropine led to a decrease in ghrelin concentrations comparable and nonadditive with breakfast ingestion and a significant decrease in both basal and meal-induced PYY concentrations. In obese subjects, atropine did not significantly change ghrelin or PYY concentrations, whereas it induced a comparable increase in heart rate and meal-induced glucose concentrations in the two study groups. Only lean, not obese, subjects experienced sustained feelings of satiety after breakfast.. The impaired cholinergic regulation of the postprandial drop in ghrelin concentrations and rise in PYY concentrations might be part of the deregulated food intake in obese subjects.

Topics: Adult; Atropine; Blood Glucose; Body Weight; Cholinergic Fibers; Cross-Over Studies; Eating; Female; Gastrointestinal Tract; Ghrelin; Heart Rate; Humans; Insulin; Insulin Resistance; Male; Obesity; Parasympatholytics; Peptide YY; Postprandial Period; Satiety Response; Vagus Nerve

Peptide YY (PYY) is released from the distal small intestine and colon after meals and reduces appetite by increasing satiety. The amount of PYY released is proportional to calories ingested. Fat ingestion has also been reported to stimulate PYY release.. The objective of the study was to determine whether macronutrient composition influences postprandial serum PYY levels by comparing 1 wk of a weight-maintenance low-carbohydrate, high-fat (LCHF) diet with a low-fat, high-carbohydrate (LFHC) diet.. In this randomized crossover study, 18 obese subjects (14 females, 4 males, mean body mass index 35.6 +/- 2.9 kg/m(2)) were randomly assigned initially to 1 wk of a weight-maintenance LCHF or LFHC diet, after which a test meal of identical composition was given and serum PYY levels were assessed for 2.5 h postprandially. After a 1-wk washout period, subjects were crossed over and retested.. After 1 wk, mean postprandial area under the curve PYY after the LCHF test meal was 1.5-fold greater than after the LFHC test meal (P < 0.001). The LCHF diet led to 55% higher levels of postprandial serum PYY levels, compared with the LFHC diet (P = 0.005).. These data show that a LCHF diet stimulates PYY secretion more than a LFHC diet in obese individuals.

Topics: Adiponectin; Adult; Blood Glucose; Body Weight; Cross-Over Studies; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Dietary Carbohydrates; Dietary Fats; Energy Intake; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period

High-fat and high-carbohydrate diets lead to insulin resistance, gastrointestinal adaptation, and high plasma triacylglycerol concentrations. It is unclear, however, how rapidly these changes occur.. We sought to determine the effects of both high-fat and high-carbohydrate evening meals on parameters of insulin resistance, hypertriglyceridemia, and gastrointestinal hormones.. Twelve healthy men were studied on 4 separate occasions. On 2 occasions, the subjects received a high-fat evening meal (62% of energy from fat) and on the other 2 occasions the subjects received a low-fat evening meal (16% of energy from fat). The morning after each meal the subjects were administered either an oral-fat-tolerance test or an oral-glucose-tolerance test. Plasma samples were analyzed for glucose, insulin, fatty acids, 3-hydroxybutyrate, triacylglycerol, pancreatic polypeptide, peptide YY, and cholecystokinin. Postchallenge data were analyzed by two-way analysis of variance with interaction and fasting concentrations analyzed by repeated-measures analysis of variance.. Fasting plasma concentrations of triacylglycerol were significantly elevated 12 h after each evening meal, but fatty acid and 3-hydroxybutyrate concentrations were reduced. No effects on glucose or insulin concentrations were detected. The high-fat evening meals elevated plasma cholecystokinin concentrations, reduced fasting concentrations of pancreatic polypeptide, and had no significant effect on peptide YY concentrations. The ratio of fat to carbohydrate in the evening meal produced significant effects on plasma triacylglycerol and fatty acids during both the oral-fat-tolerance and oral-glucose-tolerance tests.. The present study showed that the effects of high-fat and high-carbohydrate evening meals persist at least overnight and suggests that knowledge of recent dietary history is essential to the effective design of metabolic studies.

Topics: 3-Hydroxybutyric Acid; Adult; Analysis of Variance; Area Under Curve; Blood Glucose; Cholecystokinin; Dietary Carbohydrates; Dietary Fats; Energy Metabolism; Fasting; Fatty Acids; Fatty Acids, Nonesterified; Gastrointestinal Hormones; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Triglycerides

More than one-third of chronic pancreatitis patients will eventually develop diabetes, recently classified as post-chronic pancreatitis diabetes mellitus (PPDM-C). This study was aimed to investigate the pancreatic and gut hormone responses to a mixed meal test in PPDM-C patients, compared with non-diabetic chronic pancreatitis (CP), and type 2 diabetes patients or healthy controls.. Sixteen patients with PPDM-C, 12 with non-diabetic CP as well as 10 with type 2 diabetes and healthy controls were recruited. All participants underwent mixed meal tests, and blood samples were collected for measurements of blood glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, peptide YY, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). Indices of insulin sensitivity and secretion were calculated. Repeated measures analysis of variance was performed.. Participants with PPDM-C exhibited decreases in both fasting and postprandial responses of C-peptide (P < 0.001), insulin (P < 0.001), ghrelin (P < 0.001) and PYY (P = 0.006) compared to participants with type 2 diabetes and healthy controls. Patients with CP showed blunted glucagon, PP and incretin reactions, while the responses were increased in patients with PPDM-C compared to controls. The level of insulin sensitivity was higher for PPDM-C than type 2 diabetes (P < 0.01), however the indices for early/late-phase and overall insulin secretion (P < 0.01) were lower.. Patients with PPDM-C are characterized by decreased C-peptide, insulin, ghrelin and PYY responses, and similar levels of glucagon, PP, GIP and GLP-1 compared to those with type 2 diabetes. The above findings, when confirmed in a larger population, may prove helpful to establish the diagnosis of PPDM-C, and should promote study on underlying pathophysiological mechanisms.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Pancreatitis, Chronic; Peptide YY

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, β-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Food, Fortified; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose; Homeostasis; Humans; Insulin; Insulin Resistance; Lactuca; Molybdenum; Peptide YY

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (

Topics: Adenosine Deaminase; Animals; Appetite; Body Composition; Diet, High-Fat; Dyslipidemias; Eating; Ghrelin; Glucose Tolerance Test; Insulin Resistance; Male; Mice; Mice, Knockout; Obesity; Peptide YY

The aim of the present study was to assess the effect of the PYY3-36, as a potential therapy for the type 2 diabetes mellitus (T2DM), induced by high fat diet (HFD) and an intraperitoneal (i.p.) administration of streptozotocin (STZ) in albino rats.. Forty adult male albino Wistar rats were divided into: 1) control group (C, in which the rats were fed with a standard diet and received vehicle; 2) diabetic group (D, in which T2DM was induced by feeding the rats with HFD for four weeks followed by a single i.p. injection of 35 mg/kg STZ, this group was also allowed to have HFD till the end of the study; and 3) D+PYY3-36 group (in which the diabetic rats were treated with 50 µg/kg i.p. PYY3-36 twice a day for one week). Food intake, water intake, body weight (b.w.), visceral fat weight (VFW), liver glycogen content, serum levels of glucose, insulin, and interleukin-6 (IL-6), were measured. Homeostatic-model assessment of insulin resistance (HOMA-IR) was estimated. The gene expression of the hypothalamic neuropeptide Y (NPY) and visceral nuclear factor kappa B (NF-κB) were assessed by a reverse transcription polymerase chain reaction (RT-PCR).. The PYY3-36 administration to the diabetic group of rats significantly increased the serum insulin levels and liver glycogen content, decreased the body weight, VFW, food intake, water intake, serum levels of the glucose, IL-6, and HOMA-IR. It also decreased the expression of both the hypothalamic NPY and the visceral fat NF-κB.. With respect to the fact of improved insulin release and enhanced insulin sensitivity (an effect that may be mediated via suppressing accumulation of visceral fat and inflammatory markers), in the rats treated with PYY3-36, the PYY3-36 might be considered for the future as a promising therapeutic tool in T2DM.

Topics: Adiposity; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Drinking; Eating; Insulin Resistance; Intra-Abdominal Fat; Male; Organ Size; Peptide Fragments; Peptide YY; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Streptozocin

The current study aimed to assess profiles of peptide YY and ghrelin, visual analog scales (VAS) for hunger and satiety, and ad libitum intake in obese and non-obese women.. This open-label non-randomized interventional study involved obese (BMI ≥ 25-35 kg/m2) and non-obese (BMI 18.5-23.0 kg/m2) women subjects. Levels of peptide YY and ghrelin were determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA), respectively, while the degrees of hunger and satiety were measured using visual analog scale (VAS) questionnaires. The results were compared in fasting condition and in 15, 60, 120, and 180 minutes after breakfast with balance composition formulation. This study also compared the ad libitum intake within 4 hours after breakfast.. As compared to the non-obese group, the obese group have significantly lower levels of peptide YY in fasting, and in 15, 60, 120, and 180 minutes post-prandial, and smaller AUC (Area Under the Curve) of fasting peptide YY. Furthermore, the obese group showed significantly higher ad libitum intake. The obese group also have lower levels of ghrelin and lower VAS for hunger and higher in VAS for satiety as compared to the non-obese group.. There were significant differences in peptide YY level, 4 hours after breakfast ad libitum intake, ghrelin level, and VAS for hunger and satiety, between obese group and non-obese one.

Topics: Adult; Area Under Curve; Female; Ghrelin; Humans; Hunger; Indonesia; Insulin Resistance; Obesity; Peptide YY; Satiation; Visual Analog Scale

Macronutrient regulation of hyperphagia and adiposity in Prader-Willi syndrome (PWS) is poorly understood. We compared fasting and postprandial concentrations of hormones and metabolites in eight PWS children (age 9-18 years) fed, in random order, low carbohydrate, high-fat (LC, 15% carb; 65% fat; 20% protein) and low-fat, high carbohydrate (LF, 65% carb, 15% fat, 20% protein) diets matched for calories and protein.. Participants were randomized to consume either the LC or LF diet during a first hospital admission and the second diet during a subsequent admission. Blood samples were obtained after overnight fasting and 1 hour after a mixed meal.. Relative to subjects consuming the LF diet, subjects consuming the LC diet had: lower postprandial insulin concentrations (P = 0.02); higher fasting GLP-1 AND GIP concentrations and increased postprandial GLP-1 (P < 0.02); reduced ratio of fasting ghrelin to GLP-1 (P = 0.0078); increased FFA and fatty acid oxidation, as assessed by concentrations of even-chain acylcarnitines (P < 0.001); lower fasting TG and TG/HDL ratio (P < 0.01); and higher concentrations of branch chain amino acids (P < 0.01). There were no changes in glucose, PYY, or adiponectin. CRP, AST and ALT were all higher (P < 0.01) on the LC diet.. Increases in GLP-1 with low carbohydrate feeding and reductions in the ratio of ghrelin to GLP-1 might limit food intake and improve glycaemic control in PWS. Other potential benefits of carbohydrate restriction may include fat mobilization and oxidation and reductions in the TG/HDL ratio, a marker of insulin resistance. However, increases in CRP, AST and ALT necessitate longer-term studies of low carbohydrate efficacy and safety.

Topics: Adiposity; Adolescent; Amino Acids; Blood Glucose; Child; Fasting; Female; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Peptide YY; Prader-Willi Syndrome

Bariatric surgery is associated with significant and sustained weight loss and improved metabolic outcomes. It is unclear if weight loss alone is the main mechanism of improved metabolic health. The purpose of this trial was to compare indices of appetite regulation, insulin sensitivity and energy intake (EI) between participants achieving 10 kg of weight loss via Roux-en-Y Gastric Bypass (RYGB) or dietary restriction (DIET); intake of a very low calorie liquid diet (800 kcal/d; 40% protein, 40% fat, 20% carbohydrate that matched the post-RYGB dietary protocol). Adults qualifying for bariatric surgery were studied before and after 10 kg of weight loss (RYGB [n = 6]) or DIET [n = 17]). Appetite (hunger, satiety, and prospective food consumption [PFC]), appetite-related hormones, and metabolites (ghrelin, PYY, GLP-1, insulin, glucose, free fatty acids [FFA], and triglycerides [TG]) were measured in the fasting state and every 30 min for 180 min following breakfast. Participants were provided lunch to evaluate acute ad libitum EI, which was similarly reduced in both groups from pre to post weight loss. Fasting ghrelin was reduced to a greater extent following RYGB compared to DIET (P = 0.04). Area under the curve (AUC) for ghrelin (P = 0.01), hunger (P < 0.01) and PFC (P < 0.01) increased after DIET compared to RYGB, following 10 kg weight loss. Satiety AUC increased after RYGB and decreased after DIET (P < 0.01). Glucose and insulin (fasting and AUC) decreased in both groups. FFA increased in both groups, with a greater increase in AUC seen after RYGB versus DIET (P = 0.02). In summary, appetite-related indices were altered in a manner that, if maintained, may promote a sustained reduction in energy intake with RYGB compared to DIET. Future work with a larger sample size and longer follow-up will be important to confirm and extend these findings.

Topics: Adult; Appetite; Appetite Regulation; Blood Glucose; Body Mass Index; Diet, Reducing; Energy Intake; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Satiation; Weight Loss

Understanding the mechanisms underlying the remarkable beneficial effects of gastric bypass surgery is important for the development of non-surgical therapies or less invasive surgeries in the fight against obesity and metabolic disease. Although the intestinal L-cell hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) have attracted the most attention, direct tests in humans and rodents with pharmacological blockade or genetic deletion of either the GLP1-receptor (GLP1R) or the Y2-receptor (Y2R) were unable to confirm their critical roles in the beneficial effects gastric bypass surgery on body weight and glucose homeostasis. However, new awareness of the power of combinatorial therapies in the treatment of metabolic disease would suggest that combined blockade of more than one signaling pathway may be necessary to reverse the beneficial effects of bariatric surgery.. The metabolic effects of high-fat diet and the ability of Roux-en-Y gastric bypass surgery to lower food intake and body weight, as well as improve glucose handling, was tested in GLP1R and Y2R-double knockout (GLP1RKO/Y2RKO) and C57BL6J wildtype (WT) mice.. GLP1RKO/Y2RKO and WT mice responded similarly for up to 20 weeks on high-fat diet and 16 weeks after RYGB. There were no significant differences in loss of body and liver weight, fat mass, reduced food intake, relative increase in energy expenditure, improved fasting insulin, glucose tolerance, and insulin tolerance between WT and GLP1RKO/Y2RKO mice after RYGB.. Combined loss of GLP1R and Y2R-signaling was not able to negate or attenuate the beneficial effects of RYGB on body weight and glucose homeostasis in mice, suggesting that a larger number of signaling pathways is involved or that the critical pathway has not yet been identified.

Topics: Animals; Bariatric Surgery; Blood Glucose; Body Weight; Diet, High-Fat; Energy Metabolism; Gastric Bypass; Gene Expression Regulation; Glucagon-Like Peptide-1 Receptor; Insulin; Insulin Resistance; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Peptide YY; Receptors, G-Protein-Coupled; Transcriptome

The gastric mucosa is an endocrine organ that regulates satiation pathways by expression of orexigenic and anorexigenic hormones. Vertical sleeve gastrectomy (VSG) excludes gastric mucosa and reduces gastric volume. Our study aimed to investigate the independent effects of altering gastric mucosa on obesity and its related comorbidities.. Gastric mucosa devitalization (GMD) of 70% of the stomach was achieved by argon plasma coagulation in a high-fat diet rat model and was compared with VSG and sham surgery. In an 8-week follow-up study, we quantified body weight, visceral adiposity, insulin resistance index, cholesterol profiles, and free fatty acid profiles by enzyme-linked immunosorbent assay (ELISA). Following a 2-hour oral glucose tolerance test, the kinetics of ghrelin, glucagon-like peptide-1, peptide YY, and serum and liver bile acid levels were measured. Liver lipid content was quantified by ELISA.. GMD resulted in significant reductions in body weight, visceral and subcutaneous adipose tissue, and hepatic steatosis as well as an improvement in lipid metabolism. GMD resulted in significant reductions in food intake and intestinal malabsorption of free fatty acids, both contributing to improved body composition and metabolic profile. Mechanistically, GMD resulted in a significant reduction in serum palmitate levels as well as an increase in serum and liver bile acid levels, known to alter glucose and lipid metabolism. Similar changes were noted when VSG rats were compared with sham surgery rats.. Devitalization of gastric mucosa, independent of altering gastric volume, was able to reduce obesity-related comorbidities. The gastric mucosa may be a potential target for treating obesity and its associated comorbidities.

Topics: Adiposity; Animals; Argon Plasma Coagulation; Bile Acids and Salts; Blood Glucose; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Nonesterified; Gastrectomy; Gastric Mucosa; Ghrelin; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Lipid Metabolism; Liver; Male; Obesity; Peptide YY; Rats; Rats, Sprague-Dawley; Stomach; Triglycerides

To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux-en-Y gastric bypass (RYGB) and specifically the contribution of the concurrent peri-operative dietary restrictions, which may also alter glucose metabolism.. In order to assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled 10 patients with type 2 diabetes scheduled to undergo RYGB. All patients underwent a 10-day inpatient supervised dietary intervention equivalent to the peri-operative diet (diet-only period), followed by, after a re-equilibration (washout) period, an identical period of pair-matched diet in conjunction with RYGB (diet and RYGB period). We conducted extensive metabolic assessments during a 6-hour mixed-meal challenge test, with stable isotope glucose tracer infusion performed before and after each intervention.. Similar improvements in glucose levels, β-cell function, insulin sensitivity and post-meal hepatic insulin resistance were observed with both interventions. Both interventions led to significant reductions in fasting and postprandial acyl ghrelin. The diet-only intervention induced greater improvements in basal hepatic glucose output and post-meal gastric inhibitory polypeptide (GIP) secretion. The diet and RYGB intervention induced significantly greater increases in post-meal glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and glucagon levels.. Strict peri-operative dietary restriction is a main contributor to the rapid improvement in glucose metabolism after RYGB. The RYGB-induced changes in the incretin hormones GLP-1 and PYY probably play a major role in long-term compliance with such major dietary restrictions through central and peripheral mechanisms.

Topics: Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Liver; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Remission Induction

To examine the effect of different feeding routes on appetite and metabolic responses after Roux-en-Y gastric bypass (RYGB).. A standard liquid meal was administered either orally, into the gastric remnant, or intraduodenally 6 months after RYGB. Changes in plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), and appetite were measured pre- and postprandially.. Postprandial GLP-1 and PYY responses were similar, whereas glucose, insulin, and GIP levels differed markedly after oral versus intraduodenal feeding. Intraduodenal feeding prompted an intermediate appetite response (i.e., between oral and intragastric). For postprandial glucose, insulin, and GIP levels, the intraduodenal route was more similar to the intragastric than the oral route. Intragastric administration did not evoke changes in appetite, glucose, or insulin; however, it slightly increased GLP-1 and PYY and moderately increased GIP.. Appetite and metabolic responses after RYGB depend on the route by which nutrients enter the gastrointestinal tract.

Topics: Adult; Appetite; Blood Glucose; Duodenum; Enteral Nutrition; Female; Food; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Meals; Obesity; Peptide YY; Postprandial Period; Stomach

Gastric bypass surgery leads to profound changes in the secretion of gut hormones with effects on metabolism, appetite, and food intake. Here, we discuss their contributions to the improvement in glucose tolerance and the weight loss that results from the operations. We find that the improved glucose tolerance is due the following events: a negative energy balance and resulting weight loss, which improve first hepatic and later peripheral insulin sensitivity, in combination with increased postprandial insulin secretion elicited particularly by exaggerated glucagon-like peptide-1 responses. The weight loss is due to loss of appetite resulting in reduced energy intake, and we find it probable that this process is driven by exaggerated secretion of appetite-regulating gut hormones including, but probably not limited to, glucagon-like peptide-1 and peptide-YY. The increased secretion is due to an accelerated exposure to and absorption of nutrients in the small intestine. This places the weight loss and the gut hormones in key positions with respect to the metabolic improvements after bypass surgery.

Topics: Appetite; Bariatric Surgery; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Proteins; Digestion; Eating; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Intestinal Absorption; Nutrients; Obesity, Morbid; Peptide YY; Weight Loss

To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB).. SG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times.. SG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3' nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups.. HFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.

Topics: Animals; Apoptosis; Bariatric Surgery; Body Weight; Diabetes Mellitus, Experimental; Diet, High-Fat; Duodenum; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Homeostasis; Insulin; Insulin Resistance; Insulin-Secreting Cells; Jejunum; Liver; Muscles; Peptide YY; Rats; Recurrence; Remission Induction; Signal Transduction; Streptozocin

Enteroendocrine cells sense nutrients through taste receptors similar to those on the tongue. Sweet and fatty acid taste receptors (FFAR) coupled to the gustatory G-protein, gustducin, on enteroendocrine cells play a role in gut hormone release. We studied if supplementation of artificial (sucralose) or prebiotic (oligofructose; OFS) sweeteners target gustducin-mediated signaling pathways to alter gut hormone release and reduce obesity-associated disorders.. Wild-type (WT) and α-gustducin knockout (α-gust

Topics: Animals; Diet, High-Fat; Dietary Supplements; Enteroendocrine Cells; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Insulin Resistance; Male; Mice, Inbred C57BL; Mice, Knockout; Oligosaccharides; Peptide YY; Receptors, G-Protein-Coupled; Sucrose; Sweetening Agents; Transducin; Weight Gain

Apolipoprotein A-IV (ApoA-IV) has been shown to be involved in obesity and diabetes pathogenesis in animal studies, but its role in humans is uncertain.. The objective of this study was to determine the relation of ApoA-IV with changes in glucose metabolism and weight after bariatric surgery.. University Hospital.. The patients (n = 49) included lean controls (n = 8) and patients before and after a mean of 7 months after laparoscopic adjustable gastric banding (LAGB, n = 12), laparoscopic Roux-en-Y gastric bypass (RYGB, n = 22), or laparoscopic sleeve gastrectomy (SG, n = 11). ApoA-IV and other hormone assays were performed in the fasting and the postprandial state. Pearson's correlation analyses controlled for baseline BMI and percent excess weight loss (EWL) were used to determine relationships between ApoA-IV levels and insulin resistance (HOMA-IR).. With all bariatric procedures combined, the change in ApoA-IV [533 versus 518 microg/L, P = .813] or ApoA-IV area under the curve (AUC - 1072 versus 1042, P = .939) was not significant. None of the surgeries individually affected levels of fasting or ApoA-IV AUC. Bariatric surgery resulted in a decrease in HOMA-IR (5.3 versus 2.0, P<.001). In the RYGB group, higher baseline ApoA-IV levels correlated with decrease in HOMA-IR [r = -.6, P = .008]. This relationship was independent of EWL and was not observed in the LAGB or SG group. There was no association of ApoA-IV levels with EWL, insulin secretion, Peptide-YY, or leptin levels.. Preoperative ApoA-IV levels, rather than changes in levels, positively correlate with improvements in insulin sensitivity independent of weight loss after RYGB.

Topics: Adult; Apolipoproteins A; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Fasting; Female; Gastrectomy; Gastric Bypass; Gastroplasty; Humans; Insulin Resistance; Laparoscopy; Male; Obesity; Peptide YY; Postoperative Care; Postprandial Period; Preoperative Care; Weight Loss

Chronic exposure to lipopolysaccharide (LPS) contributes to metabolic abnormalities, but there has been no study to evaluate plasma LPS levels after ileal transposition (IT). We examined the effect of IT on gut hormone secretion and plasma LPS levels and their correlation with metabolic parameters.. Sprague-Dawley rats underwent either IT or sham operation. After 4 weeks, oral glucose tolerance tests (OGTT) were performed and fasting plasma LPS and gut histology were analyzed.. Compared with the sham group, food intake and body weight decreased, and insulin sensitivity increased in the IT group. During the OGTTs, glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were significantly higher in the IT group than the sham group. The villi length, muscle thickness, and the density of GLP-1 and glucose-dependent insulinotropic polypeptide co-expressing cells (K/L-cells) increased in the transposed ileum compared with the ileum of the sham group. Fasting plasma LPS levels were lower in the IT group than the sham group (5.6 ± 0.2 vs. 6.8 ± 0.1 EU/ml, P = 0.002) and significantly correlated with insulin resistance (r = 0.755, P < 0.001). Plasma LPS levels were negatively correlated with PYY secretion (r = -0.710, P = 0.001), and GLP-2 secretion (r = -0.561, P = 0.019).. IT surgery decreased plasma LPS levels in a non-obese non-diabetic rat model, which was associated with improved insulin sensitivity and increased L-cell secretion.

Topics: Animals; Blood Glucose; Body Weight; Drinking; Eating; Enteroendocrine Cells; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Ileum; Insulin Resistance; Lipopolysaccharides; Male; Obesity, Morbid; Peptide YY; Rats, Sprague-Dawley

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Topics: Animals; Blood Glucose; Drinking Water; Energy Intake; Fasting; Glucose Transporter Type 2; Insulin; Insulin Resistance; Leptin; Male; Peptide YY; Rats; Saccharin; Taste; Weight Gain; Yogurt

The prevalence of type 2 diabetes mellitus is rapidly increasing all over the world and a diet promoting reduced glycaemic excursions in the postprandial phase may help to prevent the disease. In the present study guar gum (GG) and whole grain rye flour or high amylose maize starch (HAM) was combined to design bread products giving low and sustained glycaemia. A meal study was performed with young, healthy subjects and in addition to glucose and insulin, also subjective appetite ratings and biomarkers of appetite, voluntary energy intake at a second meal and markers of fermentation were studied. The combination of GG and rye was superior with improvements in subjective appetite whereas both test products lead to improvements in biomarkers of appetite compared to the white wheat bread reference. The inclusion of GG, rye and/or HAM in bread products show great potential in lowering risk factors associated with insulin resistance and improving acute and semi-acute appetite.

Topics: Adult; Amylose; Appetite; Biomarkers; Blood Glucose; Body Mass Index; Bread; Breakfast; Energy Intake; Fatty Acids, Nonesterified; Female; Fermentation; Flour; Galactans; Gastric Inhibitory Polypeptide; Ghrelin; Humans; Insulin; Insulin Resistance; Male; Mannans; Peptide YY; Plant Gums; Postprandial Period; Risk Factors; Secale; Starch; Triticum; Whole Grains; Zea mays

Obesity and type 2 diabetes mellitus are increasing worldwide, reaching pandemic proportions. The understanding of the role of functional restriction and gut hormones can be a beneficial tool in treating obesity and diabetes. However, the exact hormonal profiles in different metabolic states and surgical models are not known.. The HIPER-1 Study is a single-centre cross-sectional study in which 240 patients (in different metabolic states and surgical models) will receive an oral mixed-meal tolerance test (OMTT). At baseline and after 30, 60 and 120 min, peptide YY and glucagon-like peptide 1 levels and glucose and insulin sensitivity will be measured. The primary end point of the study will be the area under the glucagon-like peptide 1 and peptide YY curves after the OMTT. Secondary study end points will include examination of the difference in plasma levels of the distal ileal hormones in subjects with various health statuses and in patients who have been treated with different surgical techniques.. An independent ethics committee, the Institutional Review Board of Istanbul Sisli Kolan International Hospital, Turkey, has approved the study protocol. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders.. NCT02532829; Pre-results.

Topics: Adult; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Digestive System Surgical Procedures; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Models, Anatomic; Obesity; Peptide YY; Prospective Studies; Research Design; Turkey

Both glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are gut hormones involved in energy homoeostasis. Obesity, insulin resistance and hyperglycaemia are significant confounders when GLP-1 and PYY secretion is assessed. Thus, we evaluated GLP-1 and PYY response after fat load in morbidly obese patients with different degrees of insulin resistance and glycemic status.. We studied 40 morbidly obese subjects (mean age, 40·6 ± 1·3 years; mean BMI, 53·1 ± 1·2 kg/m(2) ) divided into groups according to their glycemic status: normal fasting glucose (NFG) group, impaired fasting glucose (IFG) group and type 2 diabetes mellitus (T2D) group. NFG patients were additionally subclassified, according to the homoeostasis model assessment of insulin resistance (HOMAIR ), into a low insulin-resistance (LIR) group (HOMAIR <3·9) or a high insulin-resistance (HIR) group (HOMAIR ≥3·9).. Lipid emulsion was administered orally and measurements made at baseline and 180 min postprandially of levels of GLP-1, PYY, insulin, glucose, free fatty acids, triglycerides and leptin.. At the 180-minute postprandial reading, GLP-1 and PYY had increased in LIR-NFG subjects (41·84%, P = 0·01; 35·7%, P = 0·05; respectively), whereas no changes were observed in HIR-NFG, IFG or T2D subjects.. These results suggest that in morbidly obese subjects, both insulin resistance and abnormal glucose metabolism (IFG or T2D) impair the GLP-1 and PYY response to fat load. The implications of this attenuated enteroendocrine response should be elucidated by further studies.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon-Like Peptide 1; Homeostasis; Humans; Insulin Resistance; Lipids; Male; Middle Aged; Obesity, Morbid; Peptide YY

To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, β-cell function, and appetite.. Twenty-seven long-term smokers (n=27; nine females/18 males, 28±1 years, 22.9±0.6 kg/m(2)) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and β-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured.. AFTER 3 MONTHS' SMOKING ABSTINENCE, BODY WEIGHT, AND FAT MASS WERE INCREASED (+4 AND +22% RESPECTIVELY, P0.05) AND FASTING INSULIN SENSITIVITY DETERIORATED (QUICKI: post, 0.37±0.02 vs baseline, 0.41±0.2; P<0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after >3 months' smoking abstinence (P<0.01). Carbohydrate ingestion increased after stopping smoking (P<0.05). NPY fasting levels were increased after >3 months (P<0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged.. Smoking cessation is associated with transient metabolic changes including increased β-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.

Topics: Adult; Appetite; Body Weight; Eating; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Leptin; Male; Neuropeptide Y; Peptide YY; Smoking Cessation

To assess the rapid improvement of insulin sensitivity and β-cell function following biliopancreatic diversion with duodenal switch (BPD-DS) and determine the role played by caloric restriction in these changes.. Standard meals were administrated before and on day 3, 4, and 5 after BPD-DS to measure total caloric intake, glucose excursion, insulin sensitivity, and secretion in matched type 2 diabetes and normoglycemic (NG) subjects. In a second set of study, other subjects with type 2 diabetes had the same meal tests prior to and after a 3-day caloric restriction identical to that observed after BPD-DS and then 3 days after actually undergoing BPD-DS.. Improvement of HOMA-IR occurred at day 3 after BPD-DS in diabetes and after 3 days of caloric restriction. The disposition index (DI) improved rapidly in diabetes after BPD-DS and to a similar extent after caloric restriction. DI was higher and did not change after BPD-DS in NG. Changes in glucagon-like peptide-1, gastric inhibitory peptide, peptide tyrosine tyrosine, ghrelin, and pancreatic polypeptide levels were not associated with modulation of DI in the participants.. Caloric restriction is the major mechanism underlying the early improvement of insulin sensitivity and β-cell function after BPD-DS in type 2 diabetes.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Duodenum; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Obesity, Morbid; Peptide YY; Pilot Projects

The objective of this study was to evaluate the association between insulin-resistance and fasting levels of ghrelin and PYY in Wistar rats.. A total of 25 male Wistar rats, weighing 200-300 g, was included in this study. The animals were maintained in cages with a 12/12h light-dark cycle and fed standard chow and water ad libitum. After 12-h overnight fasting, ghrelin, PYY, insulin and glucose values were determined. Insulin resistance was assessed by means of the HOMA-IR, which was ranked and the median was used as a cut-off value to categorize insulin-resistance. HOMA-IR values equal and above 2.62 were considered insulin-resistant (IR) while values below 2.62 were considered insulin sensitive (IS). Differences between means were determined using the Student t-test. Multiple regression and Pearson's correlation test were used to evaluate the association between variables.. HOMA-IR median IQ range values for IS and IR groups were, respectively, 1.56 (0.89 - 2.16) vs. [4.06 (3.50 - 4.61); p < 0.001]. The IR group presented increased levels of fasting ghrelin, PYY and insulin respectively: [50.35 (25.99 - 74.71) pg/mL vs. 12.33 (8.77 - 15.89) pg/mL; p = 0.001]; [54.38 (37.50 - 71.26) pg/mL vs. 33.17 (22.34 - 43.99) pg/mL; p = 0.016]; [18.04 (14.48 - 21.60) uU/mL vs. 7.09 (4.83 - 9.35) uU/mL; p = 0.001]. Ghrelin, but not PYY, correlated linearly and positively with HOMA-IR: ghrelin vs. HOMA-IR (r = 0.52; p = 0.008), and PYY vs. HOMA-IR (r = 0.22; p = 0.200). This correlation was independent of body weight.. Fasting ghrelin and PYY serum levels are increased in lean, relatively insulin resistant Wistar rats, and this increase is independent of weight.

Topics: Animals; Blood Glucose; Body Weight; Cross-Sectional Studies; Fasting; Ghrelin; Insulin; Insulin Resistance; Male; Peptide Fragments; Peptide YY; Rats, Wistar; Regression Analysis

Maternal protein restriction (PR) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. A few studies have shown that this adverse programming can be reversed by dietary or hormonal therapies early in postnatal life. The objective of this study was to determine if a weaning diet high in prebiotic fiber could mitigate some of the negative effects of maternal PR, such as increased adiposity and impaired glucose tolerance. Wistar rats were fed a low- (8%) or normal- (20%) protein diet during pregnancy. Male and female pups were weaned onto control (C; 5% fiber, 20% protein) or high (prebiotic) fiber (HF; 21% wt:wt, 1:1 ratio oligofructose and inulin at 4-10 wk; 10% wt:wt, 1:1 ratio oligofructose and inulin at 10-24 wk; 17.3% protein) diets. At 24 wk of age, glucose tolerance, body composition, satiety hormones, gut microbiota, and markers of intestinal permeability were measured in the offspring. Maternal PR reduced offspring birth weight by 5% and lean mass by 9% compared with the C offspring (P < 0.007). HF-fed offspring had lower body weights and percentage body fat (∼23% in males, ∼19% in females) at 24 wk than did C offspring (P < 0.02). Compared with C pups, pups fed the HF diet had greater cecal Bifidobacterium spp. (>5-fold) and plasma concentrations of the gut trophic hormone glucagon-like peptide 2 (GLP-2) (P < 0.05). In male PR offspring fed the HF diet, insulin resistance measured by the homeostasis model assessment of insulin resistance was reduced by 81% compared with those fed the C diet (P = 0.02). In female PR offspring fed the HF diet, plasma endotoxin was greater and colonic tight junction protein 1 (Tjp1) expression was lower than in those fed the C diet. A high prebiotic fiber weaning diet mitigated increased adiposity and insulin resistance associated with maternal PR, which could improve health and decrease risk of chronic disease in offspring born to malnourished dams. However, the functional importance of sex-specific changes in markers of intestinal barrier function warrants further investigation.

Topics: Adiposity; Animals; Blood Glucose; Body Composition; Body Weight; Diet; Diet, High-Fat; Diet, Protein-Restricted; Dietary Fiber; Female; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Insulin; Insulin Resistance; Male; Maternal Nutritional Physiological Phenomena; Peptide YY; Permeability; Prebiotics; Pregnancy; Rats; Rats, Wistar; Satiation; Sex Factors; Weaning

The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY(3-36) and GLP-1(7-36 amide), on glucose homeostasis are unknown.. This study sought to investigate the acute effects of PYY(3-36) and GLP-1(7-36) amide, individually and in combination, on insulin secretion and sensitivity.. Using a frequently sampled iv glucose tolerance test (FSIVGTT) and minimal modeling, this study measured the effects of PYY(3-36) alone, GLP-1(7-36) amide alone, and a combination of PYY(3-36) and GLP-1(7-36) amide on acute insulin response to glucose (AIRg) and insulin sensitivity index (SI) in 14 overweight human volunteers, studied in a clinical research facility.. PYY(3-36) alone caused a small but nonsignificant increase in AIRg. GLP-1(7-36) amide alone and the combination of PYY(3-36) and GLP-1(7-36) amide did increase AIRg significantly. No significant differences in SI were observed with any intervention.. PYY(3-36) lacks any significant acute effects on first-phase insulin secretion or SI when tested using an FSIVGTT. Both GLP-1(7-36) amide alone and the combination of PYY3-36 and GLP-1(7-36) amide increase first-phase insulin secretion. There does not seem to be any additive or synergistic effect between PYY(3-36) and GLP-1(7-36) amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on SI.

Topics: Adult; Blood Glucose; Female; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Overweight; Peptide Fragments; Peptide YY; Young Adult

Adiponectin, visfatin, and omentin are adipokines involved in insulin sensitivity. This study aimed to determine interactions between these adipokines in subcutaneous and visceral fat and in serum, and their associations with clinical factors. Adiponectin was present at the highest levels in subcutaneous and visceral fat and serum. Subcutaneous adiponectin showed positive correlations with serum adiponectin and the quantitative insulin sensitivity check index (QUICKI). Serum adiponectin correlated positively with QUICKI and serum omentin-1 but negatively with body weight, BMI, and homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous omentin correlated positively with QUICKI but negatively with waist and hip circumferences. Serum omentin-1 correlated positively with QUICKI but negatively with body weight, BMI, waist and hip circumferences, weight gain, and HOMA-IR. Serum visfatin correlated positively with serum omentin-1 and negatively with weight gain. Serum peptide YY (PYY) levels were correlated positively with subcutaneous visfatin but negatively with visceral visfatin. Positive correlations were observed between subcutaneous expression of adiponectin, visfatin, and omentin and visceral expression of these genes. Multiple linear regression analysis showed that serum adiponectin was associated with BMI and QUICKI. Serum omentin-1 could be predicted from BMI, QUICKI, and weight gain. Weight gain, serum adiponectin, omentin-1, and DBP could be used to predict serum visfatin. In conclusion, adiponectin and omentin from subcutaneous fat displayed correlations with decreased obesity and increased insulin sensitivity while visfatin showed an association with serum PYY and weight gain. The expressions of these adipokines were correlated within each type of fat but not between different fat depots.

Topics: Adiponectin; Adult; Body Mass Index; Cytokines; Gene Expression Regulation; GPI-Linked Proteins; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Lectins; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Peptide YY; Subcutaneous Fat

Fibroblast growth factor (FGF)-19 and FGF-21 are novel metabolic regulators that improve insulin resistance and obesity in rodents. The aim of the study was to assess the effects of laparoscopic sleeve gastrectomy (LSG) on serum concentrations of FGF-19 and FGF-21 along with circulating bile acids and other relevant hormonal and biochemical parameters.. Seventeen females with obesity undergoing LSG and 15 lean healthy females were included into the study. Anthropometric and biochemical parameters, serum concentrations of FGF-19 and -21, insulin, adiponectin, leptin, C-reactive protein, resistin, amylin (total), ghrelin (active), glucagon-like peptide 1 (GLP-1, active), glucose-dependent insulinotropic peptide (GIP, total), peptide YY (PYY, total), pancreatic polypeptide (PP), and bile acids, and mRNA expression of selected adipokines and inflammatory markers in bioptic samples of subcutaneous fat were assessed at baseline and 6, 12, and 24 months after LSG.. LSG markedly decreased body weight, BMI, waist circumference, and insulin levels and improved systemic inflammation and lipid levels. FGF-19 concentrations increased and FGF-21 concentrations decreased after LSG along with increased adiponectin and decreased leptin, amylin, and ghrelin levels. GLP-1, GIP, PP, and circulating bile acids were not affected by LSG. PYY decreased significantly 24 months after surgery only. mRNA expression analysis in subcutaneous fat showed markedly reduced proinflammatory state.. Our results indicate that increased FGF-19 and decreased ghrelin concentrations could have partially contributed to the improvement of systemic inflammation and some metabolic parameters after LSG, while changes of FGF-21 are rather secondary because of weight loss.

Topics: Adiponectin; Adult; Bile Acids and Salts; Body Mass Index; C-Reactive Protein; Female; Fibroblast Growth Factors; Gastrectomy; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Leptin; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Prospective Studies; Resistin; RNA, Messenger; Subcutaneous Fat; Waist Circumference; Weight Loss

In obese patients with type 2 diabetes (T2DM), Roux-en-Y-gastric-bypass (RYGB) and sleeve gastrectomy (SLG) improve glycemic control.. The objective of this study was to investigate the mechanisms of surgery-induced T2DM improvement and role of gastrointestinal hormones. PATIENTS, SETTING, AND INTERVENTION: In 35 patients with T2DM, we performed a mixed-meal test before and 15 days and 1 year after surgery (23 RYGB and 12 SLG).. Insulin sensitivity, β-cell function, and amylin, ghrelin, PYY, pancreatic polypeptide (PP), glucagon, and glucagon-like peptide-1 (GLP-1) responses to the meal were measured.. T2DM remission occurred in 13 patients undergoing RYGB and in 7 patients undergoing SLG. Similarly in the RYGB and SLG groups, β-cell glucose sensitivity improved both early and long term (P < .005), whereas insulin sensitivity improved long term only (P < .006), in proportion to body mass index changes (P < .001). Early after RYGB, glucagon and GLP-1 responses to the meal increased, whereas the PP response decreased. At 1 year, PYY was increased, and PP, amylin, ghrelin, and GLP-1 were reduced. After SLG, hormonal responses were similar to those with RYGB except that PP was increased, whereas amylin was unchanged. In remitters, fasting GLP-1 was higher (P = .04), but its meal response was flat compared with that of nonremitters; postsurgery, however, the GLP-1 response was higher. Other hormone responses were similar between the 2 groups. In logistic regression, presurgery β-cell glucose sensitivity (positive, P < .0001) and meal-stimulated GLP-1 response (negative, P = .004) were the only predictors of remission.. RYGB and SLG have a similar impact on diabetes remission, of which baseline β-cell glucose sensitivity and a restored GLP-1 response are the chief determinants. Other hormonal responses are the consequences of the altered gastrointestinal anatomy.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Gastrectomy; Gastric Bypass; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glycemic Index; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Remission Induction

Bariatric surgery consists in duodenal exclusion from the food passage in obese patients with coexistent type 2 diabetes. Nowadays bariatric surgery is considered the most effective method of glycemic index normalization and insulin resistance reduction. Recent results on obese and non-obese rats showed remission of type 2 diabetes symptoms within few days after the surgery. The aim of the present work was to analyze the mechanisms of neuro-hormonal regulation responsible for early normalization of metabolic syndrome after bariatric surgery. In present study the concentration of selected intestinal hormones and adipokines in blood plasma and gastrointestinal tissues were analyzed. Study was conducted on Wistar rats. Animals were divided into three groups (each n=6): control (SH) shame-operated rats; animals in which visceral fat tissue was extracted (LP); and rats in which Scopinaro bariatric surgery was performed (BPD). Immunochemistry analysis of blood plasma showed decrease of insulin concentration in BPD and LP and increase of polypeptide YY (PYY) in BPD group as compared to the control. In duodenal mucosa homogenates the tendency to reduce insulin in LP and BPD group, and increase PYY and visfatin in BPD group was observed. Histometry analysis showed reduction of mucosa thickness in excluded segments of gastrointestinal tract in BPD group as compared to the SH and LP. Concluding, model studies on rats allowed better understanding of mechanisms important for early normalization of glycemic index and insulin resistance reduction in rats.

Topics: Adipokines; Animals; Apelin; Bariatric Surgery; Cytokines; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Intestine, Small; Male; Nicotinamide Phosphoribosyltransferase; Peptide YY; Rats; Rats, Wistar

Shift work is associated with circadian rhythm disorder, impaired sleep and behavioural changes, including eating habits, predisposing to obesity and metabolic dysfunctions. It involves a neuro-hormonal dysregulation of appetite towards positive energy balance, including increased ghrelin and decreased leptin, but little is known about other hormones, such as xenin, derived from the upper gut (like ghrelin), and lower gut hormones. Our objective was to compare night workers with day workers in relation to appetite-regulating hormones and other metabolic parameters.. Cross-sectional, observational study.. Twenty-four overweight women, divided into night shift workers (n = 12) and day shift workers (n = 12).. BMI, waist circumference, fat mass percentage; diet composition; Pittsburgh Sleep Quality Index; lipids; adipokines; meal tolerance test curves of glucose, insulin, ghrelin, PYY3-36, oxyntomodulin, xenin, GLP-1; insulin sensitivity (Stumvoll index).. Night workers, as compared with day workers, had greater body fat mass percentage and tendency to greater waist circumference despite similar BMI; greater energy intake; impaired sleep; lower insulin sensitivity; increased triglycerides and tendency to increased C-reactive protein; similar levels of leptin and other adipokines. Night workers had a blunted post-meal suppression of ghrelin (AUCi(0-60 min) 19·4 ± 139·9 vs -141·9 ± 9·0 ng/ml·60 min, P < 0·01); blunted rise of xenin (AUC(0-180 min) 8690·9 ± 2988·2 vs 28 504·4 ± 20 308·3 pg/ml·180 min, P < 0·01) and similar curves of PYY3-36, oxyntomodulin and GPL-1.. Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations.

Topics: Adiposity; Adult; Appetite Regulation; Cross-Sectional Studies; Digestive System; Energy Intake; Female; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Neurotensin; Overweight; Oxyntomodulin; Peptide Fragments; Peptide YY; Sleep Disorders, Circadian Rhythm; Work Schedule Tolerance

The endocannabinoid system is a potential pharmacotherapy target for obesity. However, the role of this system in human food intake regulation is currently unknown.. To test whether circulating endocannabinoids might functionally respond to food intake and verify whether these orexigenic signals are deregulated in obesity alongside with anorexigenic ones, we measured plasma anandamide (AEA), 2-arachidonoylglycerol (2-AG) and peptide YY (PYY) changes in response to a meal in 12 normal-weight and 12 non-diabetic, insulin-resistant obese individuals.. Both normal-weight and obese subjects had a significant preprandial AEA peak. Postprandially, AEA levels significantly decreased in normal-weight, whereas no significant changes were observed in obese subjects. Similarly, PYY levels significantly increased in normal-weight subjects only. No meal-related changes were found for 2-AG. Postprandial AEA and PYY changes inversely correlated with waist circumference, and independently explained 20.7 and 21.3% of waist variance. Multiple regression analysis showed that postprandial AEA and PYY changes explained 34% of waist variance, with 8.2% of the variance commonly explained.. These findings suggest that AEA might be a physiological meal initiator in humans and furthermore show that postprandially AEA and PYY are concomitantly deregulated in obesity.

Topics: Adult; Appetite Regulation; Arachidonic Acids; Body Mass Index; Cannabinoid Receptor Modulators; Eating; Endocannabinoids; Female; Glycerides; Humans; Insulin Resistance; Male; Obesity; Peptide YY; Polyunsaturated Alkamides; Postprandial Period

Ileal interposition (IT), in which the distal ileum is transposed isoperistaltically into the proximal jejunum, is considered as a procedure for metabolic or antidiabetes surgery. Our aim was to study the effects of IT on glycemic control, fat metabolism, and hormonal changes in obese rats with spontaneous diabetes.. Animals were divided into either an IT or a sham (SH) group. They underwent an oral glucose tolerance test (OGTT) before and 4 and 8 weeks after the operation. All animals were killed 10 weeks after operation for analyses of tissue weight (liver, pancreas, epididymal fat, brown fat), immunoblotting of uncoupling protein-1 (UCP1) protein in brown adipose tissue (BAT), and fasting plasma levels of glucose, insulin, glucagon-like peptide (GLP)-1, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), and leptin.. Body weight increased postoperatively in both groups compared with preoperative weight, but it did not differ between the 2 groups. Eight weeks postoperatively, integrated blood glucose levels during the OGTT were decreased in IT compared with SH (P < .05). Fasting plasma levels of insulin, GLP-1, and GIP did not differ between the 2 groups, but PYY levels were higher in the IT animals (P < .01). The weight of epididymal and BATs, homeostasis model assessment insulin resistance, and fasting plasma leptin levels were decreased in the IT group (P < .05). Expression of UCP1 was higher in IT than SH animals (P < .05).. These results suggest that IT improves glucose and lipid metabolism by decreasing insulin resistance and epididymal fat, and increased expression of UCP1 in BAT might be among the mechanisms responsible.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Comorbidity; Diabetes Mellitus; Disease Models, Animal; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Ileum; Insulin Resistance; Ion Channels; Jejunum; Leptin; Lipid Metabolism; Male; Mitochondrial Proteins; Obesity; Peptide YY; Rats, Inbred OLETF; Uncoupling Protein 1

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).. We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.. Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.. Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Topics: Adult; Appetite; C-Peptide; Cholecystokinin; Confounding Factors, Epidemiologic; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Somatostatin; Time Factors; Weight Loss

Microsomal triglyceride transfer protein (MTP) takes part in the mobilization and secretion of triglyceride-rich lipoproteins from enterocytes and hepatocytes. We investigated the effects of JTT-130, a novel intestine-specific MTP inhibitor, on high fat diet-induced obesity and glucose intolerance.. Male Sprague-Dawley rats were fed a 3.1% fat diet or a 35% fat diet with or without JTT-130 as a food admixture (0.029%). Food intake, body weight, abdominal fat, hepatic triglyceride, faecal free fatty acids and plasma levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were assessed. Plasma levels of glucose and insulin were measured during intraperitoneal glucose tolerance tests. In addition, indirect calorimetry was performed on rats fed with a 35% fat diet.. JTT-130 treatment decreased body weights, abdominal fat and hepatic triglyceride with suppression of food intake and elevation of faecal free fatty acids and plasma GLP-1 and PYY levels in rats fed with the 35% fat diet, whereas no significant effects on these parameters except for increased faecal free fatty acids were observed in rats fed with the 3.1% fat diet. JTT-130 treatment decreased plasma levels of glucose and insulin during intraperitoneal glucose tolerance tests on rats fed with the 35% fat diet, but not on rats fed with the 3.1% fat diet. JTT-130-treated rats showed increased O(2) consumption and CO(2) production on a 35% fat diet.. JTT-130 suppresses high fat diet-induced obesity and glucose intolerance with suppression of food intake and fat absorption and could be useful for prevention and treatment of obesity and obesity-related insulin resistance.

Topics: Animals; Benzamides; Biomarkers; Blood Glucose; Carrier Proteins; Diet, High-Fat; Dietary Fats; Eating; Fatty Acids; Feces; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin Resistance; Liver; Male; Malonates; Obesity; Peptide YY; Rats; Rats, Sprague-Dawley; Triglycerides

Weight-loss independent mechanisms may play an important role in the improvement of glucose homeostasis after Roux-en-Y gastric bypass (RYGB). The objective of this analysis was to determine whether RYGB causes greater improvement in glucostatic parameters as compared with laparoscopic adjustable gastric banding (LAGB) or low calorie diet (LCD) after equivalent weight loss and independent of enteral nutrient passage. Study 1 recruited participants without type 2 diabetes mellitus (T2DM) who underwent LAGB (n = 8) or RYGB (n = 9). Study 2 recruited subjects with T2DM who underwent LCD (n = 7) or RYGB (n = 7). Insulin-supplemented frequently-sampled intravenous glucose tolerance test (fsIVGTT) was performed before and after equivalent weight reduction. MINMOD analysis of insulin sensitivity (Si), acute insulin response to glucose (AIRg) and C-peptide (ACPRg) response to glucose, and insulin secretion normalized to the degree of insulin resistance (disposition index (DI)) were analyzed. Weight loss was comparable in all groups (7.8 ± 0.4%). In Study 1, significant improvement of Si, ACPRg, and DI were observed only after LAGB. In Study 2, Si, ACPRg, and plasma adiponectin increased significantly in the RYGB-DM group but not in LCD. DI improved in both T2DM groups, but the absolute increase was greater after RYGB (258.2 ± 86.6 vs. 55.9 ± 19.9; P < 0.05). Antidiabetic medications were discontinued after RYGB contrasting with 55% reduction in the number of medications after LCD. No intervention affected fasting glucagon-like peptide (GLP)-1, peptide YY (PYY) or ghrelin levels. In conclusion, RYGB produced greater improvement in Si and DI compared with diet at equivalent weight loss in T2DM subjects. Such a beneficial effect was not observed in nondiabetic subjects at this early time-point.

Topics: Adiponectin; Adult; Blood Glucose; C-Peptide; Caloric Restriction; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Laparoscopy; Male; Middle Aged; Obesity; Peptide YY; Weight Loss

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (p<0.05). The prevalence of diabetes was 72%, 46% and 30% in the highest, medium and lowest PYY(3-36) tertile (p<0.001). The PYY(3-36) concentrations (after adjustment for age, sex and body mass index) were higher in type 2 diabetics compared to subjects with impaired fasting glucose, impaired glucose tolerance and normal glucose tolerance (p<0.001 for trend). In conclusion, fasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness.

Topics: Aged; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Coronary Artery Disease; Diabetes Mellitus, Type 2; Fasting; Humans; Insulin; Insulin Resistance; Obesity; Peptide YY

The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes.. Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined.. In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups.. Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Topics: Diabetes Mellitus, Type 2; Female; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Peptide YY

Hypertension is a major health problem and is usually associated with common conditions such as obesity, which contribute to clinical cardiac dysfunction. The role of energy homeostasis hormones such as ghrelin and PYY 3-36 in cardiovascular function remains incompletely understood. Therefore, the aim of our study was to explore the potential differences in concentrations of ghrelin forms and PYY 3-36 circulating in obese patients with grade 1 and grade 2 hypertension, with higher and lower BMI and without and with insulin resistance as well as to determine whether these hormones may be associated with left ventricular hypertrophy.. A total of 142 adult subjects were studied in three subgroups: lean (BMI < 25 kg/m(2)) normotensive subjects and obese subjects (BMI 30.0-34.9 kg/m(2)), and obese subjects (BMI 35.0-39.9 kg/m(2)) under hypertensive treatment for at least 9 years. Fasting blood glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), lipid profile, urinic acid, acylated ghrelin (A-Ghr), total ghrelin (T-Ghr), and PYY 3-36 were measured. Insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). We also echocardiographically assessed left ventricular mass (LVM) index (LVMI = LVM/height(2.7)). We evaluated the association between plasma T-Ghr, A-Ghr, PYY 3-36 levels with LVMI and other measured factors using univariate and multivariate analysis.. There were significant differences between BMI, waist circumference (WC), LVMI, hs-CRP and A-Ghr/nonacylated ghrelin (NA-Ghr) ratio (in the two obese subgroups. There was no significant difference between T-Ghr, A-Ghr and PYY 3-36 levels between obese subgroups. T-Ghr and PYY 3-36 were significantly lower in obese patients than in the control group, whereas A-Ghr levels did not differ between obese and controls. A-Ghr/NA-Ghr ratio was significantly higher in patients with second-degree hypertension and BMI 35.0-39.9 kg/m(2) than in patients with first-degree hypertension and BMI 30.0-34.9 kg/m(2). There were negative associations between T-Ghr, NA-Ghr or PYY 3-36 and LVMI (r = -0.49, p = 0.0001; r = -0.47, p = 0.0001; or r = -0.18, p = 0.029, respectively) and positive association between A-Ghr/NA-Ghr ratio and LVMI (r = 0.3, p = 0.0003). T-Ghr and NA-Ghr, were associated negatively with fasting insulin (r = -0.31, p = 0.0025; and r = -0.36, p = 0.001, repectively), while A-Ghr/NA-Ghr ratio was positively associated with BMI and fasting insulin (r = 0.23, p = 0.041; r = 0.3, p = 0.0045, respectively). T-Ghr, A-Ghr, and NAGhr were also inversely related to HOMA-IR indices in obese patients (r = -0.43, p = 0.001; r = -0.32, p = 0.0359; r = -0.35, p = 0.001, respectively). In insulin-resistant obese subjects T-Ghr and NA-Ghr correlated negatively with HOMA-IR (r = -0.34, p = 0.0015; r = -0.28, p = 0.0116, respectively). LVMI was associated negatively with T-Ghr, NA-Ghr and PYY 3-36 (r = -0.49, p = 0.0001; r = -0.47, p = 0.0001; r = -0.18, p = 0.029, respectively). In addition, LVMI was positively associated with A-Ghr/NA-Ghr ratio (r = 0.30, p = 0.0003).. Plasma ghrelin forms and PYY 3-36 levels are associated with LVMI. These associations indicate a possible interaction between gut peptides and the cardiovascular system in hypertension and obesity.

Topics: Acylation; Adult; Body Mass Index; C-Reactive Protein; Female; Ghrelin; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin; Insulin Resistance; Male; Middle Aged; Multivariate Analysis; Obesity; Peptide YY; Reference Values; Waist Circumference

Black women suffer a disproportionately higher rate of obesity than their white counterparts. Reasons for this racial disparity may reflect underlying differences in the appetite suppressing peptide-YY (PYY). The PYY response to food is differentially influenced by macronutrient content but the effect of glycemic load on PYY response is unknown. This study examined whether glycemic load influences fasting and postprandial PYY levels and whether fasting and postprandial PYY levels are lower in obese black women compared to normal weight black women and to white women. Data were collected from 40 women (20 black, 20 white; 10 each normal weight vs. obese) at the University of North Carolina Clinical and Translational Research Center (CTRC). Participants completed in counterbalanced order two 4(1/2)-day weight-maintenance, mixed macronutrient high vs. low glycemic load diets followed by a test meal of identical composition. Total PYY levels were assessed before and after each test meal. Results show no differences in fasting PYY levels but significantly less postprandial PYY area under the curve (PYY(AUC)) in the group of obese black women compared to each other group (race x obesity interaction, P < 0.04). PYY(AUC) was positively related to insulin sensitivity (P < 0.004) but was not affected by glycemic load (main and interactive effects, P > 0.27). These findings indicate that postprandial PYY secretion is not affected by glycemic load but is blunted in obese black women compared with normal weight black women and with white women; additionally, they begin to address whether blunted PYY secretion contributes uniquely to the pathogenesis of obesity in black women.

Topics: Adult; Black People; Body Weight; Eating; Fasting; Female; Humans; Hyperglycemia; Insulin Resistance; Obesity; Peptide YY; Prevalence; United States; White People; Young Adult

Bile acid sequestrants (BAS) have shown antidiabetic effects in both humans and animals but the underlying mechanism is not clear. In the present study, we evaluated cholestyramine in Zucker diabetic fatty (ZDF) rats. Although control ZDF rats had continuous increases in blood glucose and hemoglobin A1c (HbA1c) and serum glucose and a decrease in serum insulin throughout a 5-week study, the cholestyramine-treated ZDF rats showed a dose-dependent decrease and normalization in serum glucose and HbA1c. An oral glucose tolerance test showed a significant increase in glucose-stimulated glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin release in rats treated with cholestyramine. Quantitative analysis of gene expression indicated that cholestyramine treatment decreased farnesoid X receptor (FXR) activity in the liver and the intestine without liver X receptor (LXR) activation in the liver. Moreover, a combination of an FXR agonist with cholestyramine did not reduce the antihyperglycemic effect over cholestyramine alone, suggesting that the FXR-small heterodimer partner-LXR pathway was not required for the glycemic effects of cholestyramine. In summary, our results demonstrated that cholestyramine could completely reverse hyperglycemia in ZDF rats through improvements in insulin sensitivity and pancreatic beta-cell function. Enhancement in GLP-1 and PYY secretion is an important mechanism for BAS-mediated antidiabetic efficacy.

Topics: Animals; Blood Glucose; Cholestyramine Resin; Diabetes Mellitus, Experimental; Gene Expression; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Resistance; Intestinal Mucosa; Liver; Liver X Receptors; Male; Obesity; Orphan Nuclear Receptors; Peptide YY; Rats; Rats, Zucker; Receptors, Cytoplasmic and Nuclear

Disturbed satiety and hunger perception in obese individuals has been reported, however data on the dynamic changes of hormonal mediators are sparse.. To evaluate the secretion pattern of insulin, ghrelin, peptide-YY (PYY), and amylin via 0 to 180 min oral glucose tolerance testing in obese and lean children.. A prospective clinical study was conducted on lean (n=9) and obese (n=20) Caucasian children of comparable age, gender, and pubertal stage. Serial blood samples were collected.. Compared to baseline, levels of acylated ghrelin showed a significant decrease in lean (p<0.05) but not in obese children. PYY increase was blunted and of shorter duration (60 min) in obese children. Amylin levels increased in both groups, and attained significantly higher levels in obese children (p<0.05).. Glucose stimulated gut hormone secretion differed between obese and lean children, and may explain the disturbed satiety observed in obese children.

Topics: Adolescent; Child; Energy Metabolism; Female; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Male; Obesity; Peptide YY

The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) Project uses comprehensive metabolic profiling to probe biochemical mechanisms of weight loss in humans. Measurements at baseline, 2 and 4 weeks, 6 and 12 months included diet, body composition, metabolic rate, hormones, and 80 intermediary metabolites measured by mass spectrometry. In 27 obese adults in a behavioral weight loss intervention, median weight decreased 13.9 lb over the first 6 months, then reverted towards baseline by 12 months. Insulin resistance (HOMA) was partially ameliorated in the first 6 months and showed sustained improvement at 12 months despite weight regain. Ghrelin increased with weight loss and reverted to baseline, whereas leptin and PYY fell at 6 months and remained persistently low. NPY levels did not change. Factors possibly contributing to sustained improvement in insulin sensitivity despite weight regain include adiponectin (increased by 12 months), IGF-1 (increased during weight loss and continued to increase during weight regain), and visceral fat (fell at 6 months but did not change thereafter). We observed a persistent reduction in free fatty acids, branched chain amino acids, and related metabolites that may contribute to improved insulin action. These findings provide evidence for sustained benefits of weight loss in obese humans and insights into mechanisms.

Topics: Adiponectin; Adult; Behavior Therapy; Biomarkers; Body Weight; Diet; Energy Metabolism; Female; Ghrelin; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Middle Aged; Neuropeptide Y; Obesity; Peptide YY; Weight Gain; Weight Loss

Topics: Animals; Bariatric Surgery; Energy Intake; Fasting; Ghrelin; Humans; Insulin Resistance; Mice; Obesity; Peptide Fragments; Peptide YY; Postprandial Period; Rats; Receptors, Gastrointestinal Hormone; Satiation

To investigate the response of serum ghrelin and PYY to oral glucose and steamed-bread load and their relationships to insulin and glucose in nonobese and obese patients with type 2 diabetes.. Ten obese subjects (Male: waist > or =90 cm, Female: waist > or =80 cm) and eleven nonobese subjects with type 2 diabetes were given oral glucose load and steamed-bread challenge in 2 consecutive days after blood glucose was controlled. The serum levels of ghrelin, PYY, insulin and glucose were measured with routine methods.. (1) Either in oral glucose or steamed-bread load tests, both fasting serum PYY and ghrelin levels of obese subjects were significantly lower than those of nonobese subjects. After taking glucose or steamed-bread, all subjects were observed the increase of PYY and ghrelin levels, which reached the peak at 30 min and 60 min respectively. However, there were no significant difference found between nonobese and obese group at 30 min, 60 min and 120 min (P=NS). (2) In all subjects, fasting serum PYY, ghrelin concentrations were inversely associated with waist circumferences and BMI but not WHR. (3) No correlations were observed between serum PYY and insulin, glucose at any time points. The ghrelin and insulin levels showed a correlation at 0 min (r = -0.591, P = 0.005), however, no correlations were found at any other time points. When comparing PYY, ghrelin AUC with the AUC of insulin and glucose, no correlations were found. (4) Ghrelin level was positively correlated with QUICKI, however, no correlation between PYY concentrations and QUICKI was noted.. In the subjects with type 2 diabetes, both PYY and ghrelin respond differently to glucose and bread, athough the calories are similar. PYY and ghrelin levels are inversely related to waist and BMI but not WHR. It is fasting ghrelin not PYY negatively associated with fasting insulin and positively with QUICKI.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Ghrelin; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Peptide YY

Gut-derived hormone peptide YY (PYY) is low in subjects with obesity and type 2 diabetes (T2D). However, it is unknown whether this is a primary defect or a consequence of metabolic disturbances. In this study, we aimed to assess whether low fasting and postprandial PYY secretion is an early defect, potentially promoting the development of obesity and T2D, and whether it is modified by macronutrient content.. Prospective cross-sectional cohort study.. Nine individuals with a strong family history of T2D (REL) and seven age and adiposity matched individuals with no family history of T2D (CON).. Metabolic studies including hyperinsulinemic-euglycemic clamp, dual X-ray absorptiometry and two meal tests containing 1000 kcal with an either high fat (76%) or high carbohydrate (76%) content.. Fasting and postprandial PYY levels were measured and analyzed for potential correlations with markers for adiposity and insulin resistance.. Insulin sensitivity was not different between REL and CON. Fasting glucose, insulin, triglycerides and PYY were also not different between groups. However, the postprandial incremental area under curve (AUC) of PYY was significantly lower in REL after the high carbohydrate (HCHO) meal (+27.3 vs +60.6% increase from baseline, P=0.038). The AUC of insulin during HCHO meal correlated negatively with both AUC and fasting level of PYY (r=-0.58 and -0.60, respectively, P<0.05).. A blunted postprandial PYY secretion is observed in a very early stage in the development of T2D in genetically susceptible individuals. This defect precedes the presence of insulin resistance and adiposity, and could therefore predispose to the development of T2D.

Topics: Adult; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Disease Progression; Enteroendocrine Cells; Epidemiologic Studies; Family Health; Female; Genetic Predisposition to Disease; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Triglycerides

PYY(3-36) is a gut-derived hormone acting on hypothalamic nuclei to inhibit food intake. We recently showed that PYY(3-36) acutely reinforces insulin action on glucose disposal in mice. We aimed to evaluate effects of PYY(3-36) on energy metabolism and the impact of chronic PYY(3-36) treatment on insulin sensitivity. Mice received a single injection of PYY(3-36) or were injected once daily for 7 days, and energy metabolism was subsequently measured in a metabolic cage. Furthermore, the effects of chronic PYY(3-36) administration (continuous and intermittent) on glucose turnover were determined during a hyperinsulinemic-euglycemic clamp. PYY(3-36) inhibited cumulative food intake for 30 min of refeeding after an overnight fast (0.29 +/- 0.04 vs. 0.56 +/- 0.12 g, P = 0.036) in an acute setting, but not after 7 days of daily dosing. Body weight, total energy expenditure, and physical activity were not affected by PYY(3-36). However, it significantly decreased the respiratory quotient. Both continuous and intermittent PYY(3-36) treatment significantly enhanced insulin-mediated whole body glucose disposal compared with vehicle treatment (81.2 +/- 6.2 vs. 77.1 +/- 5.2 vs. 63.4 +/- 5.5 micromol.min(-1).kg(-1), respectively). In particular, PYY(3-36) treatment increased glucose uptake in adipose tissue, whereas its impact on glucose disposal in muscle did not attain statistical significance. PYY(3-36) treatment shifts the balance of fuel use in favor of fatty acids and enhances insulin sensitivity in mice, where it particularly promotes insulin-mediated glucose disposal. Notably, these metabolic effects of PYY(3-36) remain unabated after chronic administration, in contrast to its anorexic effects.

Topics: Animals; Blood Glucose; Dose-Response Relationship, Drug; Drug Administration Schedule; Energy Metabolism; Fatty Acids, Nonesterified; Glucose; Insulin; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Organ Specificity; Oxygen Consumption; Peptide Fragments; Peptide YY

Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Adipokines and insulin play an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown.. The aim of the study was to determine whether adipokines and insulin are independently associated with measures of BMD in adolescents with AN and controls.. Levels of adiponectin and insulin, fasting and after oral glucose, were evaluated in 17 AN patients and 19 controls (age, 12-18 yr), in whom hormonal parameters [GH, IGF-I, cortisol, estradiol, leptin, ghrelin, and peptide YY (PYY)] had been previously determined. Body composition, bone mineral content, and BMD at the lumbar spine, hip, femoral neck, and total body were assessed by dual energy x-ray absorptiometry. Two bone formation and bone resorption markers were examined.. The study was conducted at a General Clinical Research Center.. Adiponectin differed between AN subjects and controls after controlling for fat mass and decreased in both after oral glucose (P = 0.02 and 0.07). On regression modeling, independent associations were observed of: 1) body mass index and adiponectin with lumbar spine bone mineral apparent density Z-scores (r(2) = 0.45); 2) lean mass, PYY, and ghrelin with hip Z-scores (r(2) = 0.55); 3) adiponectin and lean mass with femoral neck-bone mineral apparent density Z-scores (r(2) = 0.34); and 4) lean mass, PYY, GH, and ghrelin with total body-bone mineral content/height Z-scores (r(2) = 0.64), for the combined group. Adiponectin was also independently associated with BMD, and insulin was associated with bone turnover markers in the groups considered separately.. Adiponectin contributes significantly to the variability of bone density, and insulin contributes to bone turnover markers in adolescent girls.

Topics: Adiponectin; Adolescent; Anorexia Nervosa; Blood Glucose; Body Composition; Bone and Bones; Bone Density; Estradiol; Female; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Peptide YY; Regression Analysis; Weight Gain

Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely

Topics: Acylation; Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholecystokinin; Cholesterol, LDL; Fasting; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Morbid; Peptide Hormones; Peptide YY; Poland; Postprandial Period

Topics: Animals; Eating; Gastric Emptying; Insulin Resistance; Mice; Peptide Fragments; Peptide YY; Rats; Weight Gain

Surgically induced weight loss results in reduction of comorbidities in severely obese humans. Reversal of abnormal secretion of appetite-regulating gut hormones such as peptide YY (PYY) could be contributing to the improvement of cardiovascular risk factors.. Severely obese patients (n = 42, BMI = 45.7 +/- 5.3 kg/m(2)) underwent clinical examination and blood sampling for measurement of PYY, plasma lipids, oral glucose tolerance testing and assessment of insulin secretion (HOMA-%B) and action (HOMA-R, QUICKI) before and during 12 months following gastric banding. Comparisons were made at each time point of the study as well as across the total study period.. Weight loss after bariatric surgery resulted in improvement of insulin resistance by 54% (p < 0.03) and plasma triglycerides by 26% (p < 0.01) without changes in fasting PYY (16.2 +/- 8.7 pmol/l at baseline, 15.1 +/- 6.3 pmol/l at 12 months). Fasting PYY correlated negatively with plasma total cholesterol at baseline (p = 0.02) but was not associated with body weight, body mass or abdominal diameter. Individual changes in PYY (DeltaPYY) related to changes in insulin (Deltafasting insulin) at 12 months (r = -0.582, p = 0.02) and HOMA-B at 6 months (r = -0.677, p = 0.006) and 12 months (r = -0.660, p = 0.007). Diabetic status had no impact on these correlations.. PYY correlates with a major cardiovascular risk factor and surrogate parameters of insulin secretion but not to weight loss or body mass in severe obesity.

Topics: Adult; Analysis of Variance; Cardiovascular Diseases; Fasting; Female; Follow-Up Studies; Gastroplasty; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Peptide YY; Risk Factors; Time Factors; Weight Loss

Prader-Willi syndrome (PWS) is a genetic syndrome characterized by relative hypoinsulinaemia and normal or increased insulin sensitivity despite profound obesity. We hypothesized that this increased insulin sensitivity is mediated by increased levels of total and high molecular weight adiponectin and associated with changes in levels of satiety hormones.. We measured total adiponectin and its isoforms [high molecular weight (HMW), middle molecular weight (MMW) and low molecular weight (LMW) adiponectin] and satiety hormones in 14 children with PWS [median age 11.35 years, body mass index (BMI) Z-score 2.15] and 14 BMI-matched controls (median age 11.97 years, BMI Z-score 2.34).. Despite comparable BMI Z-scores and leptin levels, the PWS children exhibited lower fasting insulin and HOMA-IR (homeostasis model assessment of insulin resistance) scores compared to obese controls. For any given BMI Z-score, the PWS children showed higher concentrations of fasting total and HMW adiponectin and higher HMW/total adiponectin ratios. The HMW/total adioponectin ratio was preserved in children with PWS at high degrees of obesity. In PWS children, fasting plasma total adiponectin, HMW adiponectin and HMW/total adiponectin ratio correlated negatively with age (P < 0.05), HOMA-IR (P < 0.01), BMI Z-score (P < 0.05), insulin (P < 0.01) and leptin (P < 0.05). In addition to higher fasting ghrelin concentrations, the PWS children showed significantly higher fasting levels of total peptide YY (PYY) and gastric inhibitory polypeptide (GIP) compared to obese controls.. Relative to controls of similar age and BMI Z-score, the PWS children had significantly higher levels of total and HMW adiponectin, and increased ratios of HMW/total adiponectin. These findings may explain in part the heightened insulin sensitivity of PWS children relative to BMI-matched controls.

Topics: Adiponectin; Adolescent; Child; Female; Gastric Inhibitory Polypeptide; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Molecular Weight; Peptide Hormones; Peptide YY; Prader-Willi Syndrome; Protein Isoforms; Thyrotropin; Thyroxine

Obesity prevalence is higher in African-American (AA) vs. American white (AW) youth. Ghrelin is a "hunger" peptide that is high preprandially and decreases postprandially, and peptide YY (PYY) is a "satiety" hormone increasing after meals. Impaired regulation of ghrelin/PYY may be conducive to obesity. We hypothesized that racial differences in childhood obesity could partly be explained by differences in ghrelin/PYY dynamics.. We investigated: 1) ghrelin suppression/PYY elevation in response to an oral glucose tolerance test (OGTT) in AA vs. AW, and 2) the relationship of ghrelin and PYY dynamics to insulin sensitivity. Thirty-three AA and 54 AW prepubertal children underwent an OGTT measuring ghrelin, PYY, glucose, and insulin. Fasting glucose to insulin ratio (G(F)/I(F)) was used to assess the relationship of insulin sensitivity to fasting and post-OGTT ghrelin and PYY levels.. OGTT-induced suppression in ghrelin (Delta ghrelin) was lower in AA youth. Delta ghrelin correlated with G(F)/I(F) (r = 0.47, P < 0.001) and Delta insulin at 30 min (r = -0.47, P < 0.001). In multiple regression analysis, race (P = 0.013) and G(F)/I(F) (P = 0.004) contributed independently to the variance in Delta ghrelin (R(2) = 0.28, P < 0.001). Fasting and post-OGTT PYY levels were lower in AAs and were not related to insulin sensitivity.. The lower suppression of ghrelin in AA, but not the lower PYY levels, correlates with insulinemia and insulin resistance. Less ghrelin suppression and PYY elevation after a meal in black youth could be a potential mechanism of race-related differences in hunger/satiety predisposing to risk of obesity.

Topics: Black or African American; Blood Glucose; Body Composition; Body Mass Index; Child; Fasting; Female; Ghrelin; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Obesity; Peptide Hormones; Peptide YY; Racial Groups; Regression Analysis; White People

Low circulating peptide YY (PYY) levels are reported in obese and type II diabetic subjects and results from PYY knockout animals suggests that PYY deficiency may have a causative role in the etiology of obesity and type 2 diabetes. Here, our aims were to determine whether people with a genetic predisposition to developing type 2 diabetes and obesity differ from otherwise similar subjects without such family history, in fasting or meal-related PYY levels, fasting insulin, insulin secretion (HOMA-B) and insulin sensitivity. We also investigated whether PYY ablation affects the intrinsic ability of islets to secrete insulin, which may be a contributing factor to the hyperinsulinemia observed in PYY knockout mice. Healthy female first-degree relatives of people with type 2 diabetes were matched for age, gender and BMI to control subjects but had significantly lower insulin sensitivity (p<0.05). Relatives also had significantly lower fasting serum PYY levels than controls (p<0.05), but their PYY response to a high fat meal (4250 kJ, 73% fat) was not significantly different. Fasting PYY level correlated positively with glucose infusion rate (r=0.713, p=0.002) and fasting adiponectin (r=0.5, p=0.02). Islets of Langerhans from PYY knockout mice were found to hypersecrete insulin in response to 25 mM glucose (p<0.05). These data demonstrate that lack of PYY enhances insulin secretion from the Islets of Langerhans and that low fasting PYY levels are associated with insulin resistance in humans. Together, these findings suggest that low circulating levels of PYY could contribute to hyperinsulinemia and insulin resistance, and possibly contribute to subsequent development of obesity and type 2 diabetes.

Topics: Adiponectin; Adiposity; Adult; Animals; Diabetes Mellitus, Type 2; Dietary Fats; Female; Glucose; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Mice; Mice, Knockout; Middle Aged; Peptide YY; Radioimmunoassay

The cause of the unique elevation in fasting plasma levels of the orexigenic gastric hormone ghrelin in many patients with Prader-Willi syndrome (PWS) is unclear. We measured fasting and postprandial plasma ghrelin in nonobese (n = 16 fasting and n = 8 postprandial) and obese non-PWS adults (n = 16 and 9), adults with genetically confirmed PWS (n = 26 and 10), and patients with hypothalamic obesity from craniopharyngioma tumors (n = 9 and 6). We show that 1) plasma ghrelin levels decline normally after food consumption in PWS, but there is still fasting and postprandial hyperghrelinemia relative to the patient's obesity (2.0-fold higher fasting ghrelin, 1.8-fold higher postprandial ghrelin, adjusting for percentage of body fat); 2) the fasting and postprandial hyperghrelinemia in PWS appears to be at least partially, but possibly not solely, explained by the concurrent relative hypoinsulinemia and preserved insulin sensitivity for the patient's obesity (residual 1.3- to 1.6-fold higher fasting ghrelin, 1.2- to 1.5-fold higher postprandial ghrelin in PWS, adjusting for insulin levels or homeostasis model assessment of insulin resistance); 3) hyperghrelinemia and hypoinsulinemia are not found in craniopharyngioma patients with hypothalamic obesity, and indeed, these patients have relative hyperinsulinemia for their obesity; and 4) there is no deficiency of the anorexigenic intestinal hormone peptide YY(3-36) in PWS contributing to their hyperghrelinemia.

Topics: Adult; Craniopharyngioma; Fasting; Female; Ghrelin; Humans; Hyperphagia; Hypothalamus; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Peptide Fragments; Peptide Hormones; Peptide YY; Pituitary Neoplasms; Postprandial Period; Prader-Willi Syndrome

Anorexia and weight loss are negative prognostic factors in patients with cancer. Although total ghrelin levels are increased in energy-negative states, levels of the biologically active octanoylated ghrelin and the anorexigenic peptide YY (PYY) have not been reported in patients with cancer-induced cachexia. We hypothesized that abnormal ghrelin and/or PYY levels contribute to cancer-induced cachexia. We evaluated 21 patients with cancer-induced cachexia; 24 cancer patients without cachexia; and 23 age-, sex-, race-, and BMI-matched subjects without cancer. Active ghrelin levels and the active to total ghrelin ratio were significantly increased in subjects with cancer-induced cachexia, compared with cancer and noncancer controls. PYY levels were similar among groups. Appetite measured by a visual analog scale was not increased in subjects with cachexia. The increase in active ghrelin levels is likely to be a compensatory response to weight loss. Cachexia may be a state of ghrelin resistance because appetite does not correlate with ghrelin levels. Changes in the active to total ghrelin ratio suggest that a mechanism other than increased secretion must be responsible for the increase in active ghrelin levels. PYY is unlikely to play an important role in cancer-induced cachexia.

Topics: Aged; Appetite; Cachexia; Ghrelin; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Interleukin-6; Middle Aged; Neoplasms; Peptide Hormones; Peptide YY; Serum Albumin; Tumor Necrosis Factor-alpha

To observe changes of plasma peptide YY (PYY) in acupuncture for slimming.. Thirty-four cases of simple obesity were treated with acupuncture for 3 courses. Body mass index (BMI), and fat percent (F%), and insulin, PYY, blood fat, and blood sugar levels before and after treatment were determined, with 20 normal persons used as controls.. The clinical total effective rate was 88.23%. Acupuncture could increase the decreased insulin sensitive index and PYY level (both P < 0.01), with no correlativity between them (P > 0.05).. Regulation of PYY is possibly one of the mechanisms of acupuncture in slimming, but the relation of PPY with insulin resistance remains to be studied.

Topics: Body Mass Index; Humans; Insulin; Insulin Resistance; Obesity; Peptide YY

Neuropeptide Y (NPY) is involved in the central regulation of appetite, sexual behavior, and reproductive function. We have previously shown that chronic infusion of NPY into the lateral ventricle of normal rats produced an obesity syndrome characterized by hyperphagia, hyperinsulinism and collapse of reproductive function. We further demonstrated that acute inhibition of LH secretion in castrated rats was preferentially mediated by the NPY receptor subtype 5 (Y(5)). In the present study, the effects of chronic, central infusion of NPY, or the mixed Y2-Y5 agonist PYY(3-36), were evaluated both in normal male C57BL/6J mice and Sprague-Dawley rats. After a 7-day infusion to male mice, both NPY and PYY(3-36) at 5 nmol per day, induced marked hyperphagia leading to significant increases in body and fat pad weights. Furthermore, both compounds markedly reduced several markers of the reproductive axis. In the rat study, PYY(3-36) was more active than NPY to inhibit the pituitary-testicular axis, confirming the importance of the Y5 subtype for such effects. In the mouse, chronic NPY infusion induced a sustained increase in corticosterone and insulin secretion. Plasma leptin levels were also markedly increased possibly explaining the observed reduction in gene expression for hypothalamic NPY. Gene expression for hypothalamic POMC was reduced in the NPY- or PYY(3-36)-infused mice, suggesting that NPY exacerbated food intake by both acting through its own receptor(s), and reducing the satiety signal driven by the POMC-derived alpha-MSH. The present study in the mouse suggests in analogy with available rat data, that constant exposure to elevated NPY in the hypothalamic area unabatedly enhances food intake leading to an obesity syndrome including increased adiposity, insulin resistance, hypercorticism, and hypogonadism, reminiscent of the phenotype of the ob/ob mouse, that displays elevated hypothalamic NPY secondary to lack of leptin negative feedback action.

Topics: Animals; Hyperphagia; Hypogonadism; Insulin Resistance; Lateral Ventricles; Leptin; Male; Mice; Mice, Inbred C57BL; Neuropeptide Y; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Sprague-Dawley; Syndrome