oxytocin and Diabetes-Mellitus--Type-2

Oxytocin was once understood solely as a neuropeptide with a central role in social bonding, reproduction, parturition, lactation and appetite regulation. Recent evidence indicates that oxytocin enhances glucose uptake and lipid utilization in adipose tissue and skeletal muscle, suggesting that dysfunction of the oxytocin system could underlie the pathogenesis of insulin resistance and dyslipidaemia. Murine studies revealed that deficiencies in oxytocin signalling and oxytocin receptor expression lead to obesity despite normal food intake, motor activity and increased leptin levels. In addition, plasma oxytocin concentration is notably lower in obese individuals with diabetes, which may suggest an involvement of the oxytocin system in the pathogenesis of cardiometabolic disease. More recently, small scale studies demonstrated that intranasal administration of oxytocin was associated with significant weight loss as well as improvements in insulin sensitivity and pancreatic β-cell responsivity in human subjects. The multi-pronged effects of oxytocin signalling on improving peripheral insulin sensitivity, pancreatic function and lipid homeostasis strongly suggest a role for this system as a therapeutic target in obesity and diabetes management. The complexity of obesity aetiology and the pathogenesis of obesity-related metabolic complications underscore the need for a systems approach to better understand the role of oxytocin in metabolic function.

Topics: Adipose Tissue; Animals; Diabetes Mellitus, Type 2; Disease Management; Energy Metabolism; Homeostasis; Humans; Insulin Resistance; Obesity; Oxytocin

Cardiovascular disease (CVD) remains the leading cause of death worldwide, despite multiple treatment options. In addition to elevated lipid levels, oxidative stress and inflammation are key factors driving atherogenesis and CVD. New strategies are required to mitigate risk and most urgently for statin-intolerant patients. The neuropeptide hormone oxytocin, synthesized in the brain hypothalamus, is worthy of consideration as a CVD ancillary treatment because it moderates factors directly linked to atherosclerotic CVD such as inflammation, weight gain, food intake and insulin resistance. Though initially studied for its contribution to parturition and lactation, oxytocin participates in social attachment and bonding, associative learning, memory and stress responses. Oxytocin has shown promise in animal models of atherosclerosis and in some human studies as well. A number of properties of oxytocin make it a candidate CVD treatment. Oxytocin not only lowers fat mass and cytokine levels, but also improves glucose tolerance, lowers blood pressure and relieves anxiety. Further, it has an important role in communication in the gut-brain axis that makes it a promising treatment for obesity and type 2 diabetes. Oxytocin acts through its receptor which is a class I G-protein-coupled receptor present in cells of the vascular system including the heart and arteries. While oxytocin is not used for heart disease at present, residual CVD risk remains in a substantial portion of patients despite multidrug regimens, leaving open the possibility of using the endogenous nonapeptide as an adjunct therapy. This review discusses the possible role for oxytocin in human CVD prevention and treatment.

Topics: Animals; Atherosclerosis; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Hypothalamus; Inflammation; Male; Oxytocin

The neurohypophysial endocrine system is identified here as a potential target for therapeutic interventions toward improving obesity-related metabolic dysfunction, given its coinciding pleiotropic effects on psychological, neurological and metabolic systems that are disrupted in obesity.. Copeptin, the C-terminal portion of the precursor of arginine-vasopressin, is positively associated with body mass index and risk of type 2 diabetes. Plasma oxytocin is decreased in obesity and several other conditions of abnormal glucose homeostasis. Recent data also show non-classical tissues, such as myocytes, hepatocytes and β-cells, exhibit responses to oxytocin and vasopressin receptor binding that may contribute to alterations in metabolic function. The modulation of anorexigenic and orexigenic pathways appears to be the dominant mechanism underlying the effects of oxytocin and vasopressin on body weight regulation; however, there are apparent limitations associated with their use in direct pharmacological applications. A clearer picture of their wider physiological effects is needed before either system can be considered for therapeutic use.

Topics: Animals; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Gastrointestinal Microbiome; Glucose; Hepatocytes; Homeostasis; Humans; Insulin Resistance; Lipid Metabolism; Muscle Cells; Obesity; Oxytocin; Vasopressins

Oxytocin is associated mainly with modulating reproductive function. However, studies suggest that oxytocin also plays a role in endocrine pancreatic function. In the present study, islet expression of oxytocin and its related receptor was confirmed in mouse islets as well as cultured rodent and human beta-cells. Oxytocin significantly stimulated glucose-induced insulin secretion from isolated mouse islets. Similar insulinotropic actions were also observed in rodent BRIN BD11 and human 1.1B4 beta-cells. Positive effects of oxytocin on insulin secretion were almost fully annulled by the oxytocin receptor antagonist, atosiban. In terms of mechanism of insulin secretory action, oxytocin had no effect on beta-cell membrane potential or cAMP generation, but did augment intracellular calcium concentrations. In vivo administration of oxytocin to mice significantly reduced overall blood glucose levels and increased plasma insulin concentrations in response to a glucose challenge. Oxytocin also had a modest, but significant, appetite suppressive effect. As expected, streptozotocin diabetic mice had marked loss of beta-cell area accompanied by increases in alpha-cell area, whilst hydrocortisone treatment increased beta-cell and overall islet areas. Both mouse models of diabetes presented with dramatically decreased percentage islet oxytocin co-localisation with insulin and increased co-localisation with glucagon. More detailed studies in cultured beta-cell lines revealed direct positive effects of oxytocin on beta-cell proliferation and protection against apoptosis. Together, these data highlight a potentially important role of islet-derived oxytocin and related receptor signalling pathways on the modulation of beta-cell function and survival.

Topics: Animals; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose; Humans; Insulin; Insulin-Secreting Cells; Mice; Oxytocin; Signal Transduction

The psychotropic mediator and neuropeptide hormone oxytocin (OXT) is emerging as a promising treatment of metabolic disorders (obesity and dysglycemia). This review focuses on studies relevant to OXT use and its mechanisms of action in metabolic disorders and wellness behavior motivation.. Randomized controlled trials (RCTs) and cohort and preclinical studies identified in electronic databases were reviewed.. There were only a few RCTs and cohort studies related to OXT and metabolic disorders. Anorexigenic and weight-loss effects of intranasal OXT (IOXT) were evaluated in 3 double-blind RCTs involving 85 subjects. A single dose of 24 IU reduced caloric intake by 122 kcal. The 24 IU 4-times daily dose for 8 weeks produced ~9-kg weight loss (P<.001 vs. placebo) and a trend toward reduced postprandial glucose and insulin levels. Similarly, in a double-blind RCT IOXT versus placebo increased the willingness to cooperate and the expectation that others will cooperate at prosocial tasks. A cohort study showed lower serum OXT level in obese versus normal-weight subjects and a negative correlation with body mass index. Circulating OXT was also lower in type 2 diabetes versus normoglycemic subjects and negatively correlated with glycosylated hemoglobin A1C and insulin resistance.. The gap of knowledge remains on the efficacy of OXT for metabolic indications. It is a challenge to the scientific community to provide data that can be disseminated to inform the scientific community, medical personnel, and the public about the potential benefits and risks of chronic OXT use.. CNS = central nervous system DM1 = diabetes mellitus type 1 DM2 = diabetes mellitus type 2 GDM = gestational diabetes mellitus GI = gastrointestinal GMB = gut microbiota IOXT = intranasal oxytoxcin OXT = oxytocin OXTR = oxytocin receptor sOXT = serum oxytocin.

Topics: Animals; Cohort Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Energy Metabolism; Humans; Obesity; Oxytocin; Randomized Controlled Trials as Topic

The gut microbiota is known to be related to type 2 diabetes (T2D), psychiatric conditions, and opioid use. In this study, we tested the hypothesis that variability in gut microbiota in T2D is associated with psycho-metabolic health.. A cross-sectional study was conducted among African American men (AAM) (n = 99) that were outpatients at a Chicago VA Medical Center. The main outcome measures included fecal microbiota ecology (by 16S rRNA gene sequencing), psychiatric disorders including opioid use, and circulating leptin and oxytocin as representative hormone biomarkers for obesity and psychological pro-social behavior.. The study subjects had prevalent overweight/obesity (78%), T2D (50%) and co-morbid psychiatric (65%) and opioid use (45%) disorders. In the analysis of microbiota, the data showed interactions of opioids, T2D and metformin with Bifidobacterium and Prevotella genera. The differential analysis of Bifidobacterium stratified by opioids, T2D and metformin, showed significant interactions among these factors indicating that the effect of one factor was changed by the other (FDR-adjusted p [q] < 0.01). In addition, the pair-wise comparison showed that participants with T2D not taking metformin had a significant 6.74 log2 fold increase in Bifidobacterium in opioid users as compared to non-users (q = 2.2 x 10-8). Since metformin was not included in this pair-wise comparison, the significant 'q' suggested association of opioid use with Bifidobacterium abundance. The differences in Bifidobacterium abundance could possibly be explained by opioids acting as organic cation transporter 1 (OCT1) inhibitors. Analysis stratified by lower and higher leptin and oxytocin (divided by the 50th percentile) in the subgroup without T2D showed lower Dialister in High-Leptin vs. Low-Leptin (p = 0.03). Contrary, the opposite was shown for oxytocin, higher Dialister in High-Oxytocin vs. Low-Oxytocin (p = 0.04).. The study demonstrated for the first time that Bifidobacterium and Prevotella abundance was affected by interactions of T2D, metformin and opioid use. Also, in subjects without T2D Dialister abundance varied according to circulating leptin and oxytocin.

Topics: Bacteria; Black or African American; Chronic Disease; Cost of Illness; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Humans; Leptin; Male; Metformin; Opioid-Related Disorders; Oxytocin

Obesity is important for the development of type-2 diabetes as a result of obesity-induced insulin resistance accompanied by impaired compensation of insulin secretion from pancreatic beta cells. Here, based on a randomized pilot clinical trial, we report that intranasal oxytocin administration over an 8-week period led to effective reduction of obesity and reversal of related prediabetic changes in patients. Using mouse models, we further systematically evaluated whether oxytocin and its analogs yield therapeutic effects against prediabetic or diabetic disorders regardless of obesity. Our results showed that oxytocin and two analogs including [Ser4, Ile8]-oxytocin or [Asu1,6]-oxytocin worked in mice to reverse insulin resistance and glucose intolerance prior to reduction of obesity. In parallel, using streptozotocin-induced diabetic mouse model, we found that treatment with oxytocin or its analogs reduced the magnitude of glucose intolerance through improving insulin secretion. The anti-diabetic effects of oxytocin and its analogs in these animal models can be produced similarly whether central or peripheral administration was used. In conclusion, oxytocin and its analogs have multi-level effects in improving weight control, insulin sensitivity and insulin secretion, and bear potentials for being developed as therapeutic peptides for obesity and diabetes.

Topics: Administration, Intranasal; Adult; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Middle Aged; Obesity; Oxytocin; Pilot Projects; Prediabetic State; Young Adult

The results of treatment of 90 patients with diabetes mellitus and pyo-necrotic lesions of the feet were compared. Oxytocin was used in 40 of the patients. It was found that parenteral administration of oxytocin resulted in more favorable course of diabetes mellitus in such patients. The intra-arterial or local use of Oxytocin was found to reliably increase the DNA synthesis by the endothelial cells, fibroblasts and histiocytes, which in its turn creates favorable conditions for the reparative process in the wounds and allows quality of the treatment to be considerably improved.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Chronic Disease; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Foot; DNA; Female; Foot; Humans; Male; Middle Aged; Necrosis; Oxytocin

Oxytocin (OXT) controls appetite, promotes diet-induced energy expenditure, and may protect against obesity. Furthermore, the oxytocin system controls ovarian follicle luteinization and steroidogenesis as well as adrenal steroidogenesis, which if impaired might lead to anovulation and hyperandrogenism, signs found in women with polycystic ovarian syndrome (PCOS). PCOS is a common complex endocrine disorder of reproductive-age women, and it often presents with impaired glucose metabolism, insulin resistance (IR), and type 2 diabetes (T2D). The oxytocin receptor gene (OXTR) may confer a risk for PCOS, conceivably through dysregulation of metabolism, ovarian follicle maturation, and ovarian and adrenal steroidogenesis. Therefore, we aimed to investigate whether OXTR variants confer risk for PCOS.. In 212 Italian subjects with T2D and PCOS, we have analyzed 22 single nucleotide polymorphisms (SNPs) within the OXTR gene for linkage to and/or linkage disequilibrium (LD, i.e., association) with PCOS. We tested whether the significant risk variants were independent or part of an LD block.. We found 5 independent variants significantly linked to/in LD with PCOS within the peninsular families.. This is the first study to report OXTR as a novel risk gene in PCOS. Functional and replication studies are needed to confirm these results.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hyperandrogenism; Insulin Resistance; Oxytocin; Polycystic Ovary Syndrome; Receptors, Oxytocin

The oxytocin system is well-known for its role in social bonding and reproduction. Recently, the oxytocin system was found to play other metabolic roles such as regulation of food intake, peripheral glucose uptake, and insulin sensitivity. Variants in

Topics: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; Oxytocin; Polymorphism, Single Nucleotide; Receptors, Oxytocin

Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus (T2DM). To address this, we investigated the neuronal and glial populations in the PVN of 26 T2DM patients and 20 matched controls. Our findings revealed a significant reduction in oxytocin (Oxt) neuron density in the PVN of T2DM patients compared to controls, while other neuronal populations remained unchanged. This suggests that Oxt neurons may play a specific role in the pathophysiology of T2DM. Interestingly, the reduction in Oxt neurons was accompanied by a decreased melanocortinergic input in to the PVN as reflected by a reduction in alpha-MSH immunoreactivity. We also analysed two glial cell populations, as they are important for maintaining a healthy neural microenvironment. We found that microglial density, phagocytic capacity, and their proximity to neurons were not altered in T2DM patients, indicating that the loss of Oxt neurons is independent of changes in microglial immunity. However, we did observe a reduction in the number of astrocytes, which are crucial for providing trophic support to local neurons. Moreover, a specific subpopulation of astrocytes characterized by aquaporin 4 expression was overrepresented in T2DM patients. Since this subset of astrocytes is linked to the glymphatic system, their overrepresentation might point to alterations in the hypothalamic waste clearance system in T2DM. Our study shows selective loss of Oxt neurons in the PVN of T2DM individuals in association with astrocytic reduction and gliovascular remodelling. Therefore, hypothalamic Oxt neurons may represent a potential target for T2DM treatment modalities.

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus

Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists have been approved for the treatment of type 2 diabetes mellitus (T2DM); however, the brain actions of these drugs are not properly established. We used post mortem microdissected human hypothalamic samples for RT-qPCR and Western blotting. For in situ hybridization histochemistry and immunolabelling, parallel cryosections were prepared from the hypothalamus. We developed in situ hybridization probes for human GLP-1R and oxytocin. In addition, GLP-1 and oxytocin were visualized by immunohistochemistry. Radioactive in situ hybridization histochemistry revealed abundant GLP-1R labelling in the human paraventricular hypothalamic nucleus (PVN), particularly in its magnocellular subdivision (PVNmc). Quantitative analysis of the mRNA signal demonstrated increased GLP-1R expression in the PVNmc in post mortem hypothalamic samples from T2DM subjects as compared to controls, while there was no difference in the expression level of GLP-1R in the other subdivisions of the PVN, the hypothalamic dorsomedial and infundibular nuclei. Our results in the PVN were confirmed by RT-qPCR. Furthermore, we demonstrated by Western blot technique that the GLP-1R protein level was also elevated in the PVN of T2DM patients. GLP-1 fibre terminals were also observed in the PVNmc closely apposing oxytocin neurons using immunohistochemistry. The data suggest that GLP-1 activates GLP-1Rs in the PVNmc and that GLP-1R is elevated in T2DM patients, which may be related to the dysregulation of feeding behaviour and glucose homeostasis in T2DM.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Oxytocin; Paraventricular Hypothalamic Nucleus

Oxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin's role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses.

Topics: Biological Specimen Banks; Diabetes Mellitus, Type 2; Humans; Mental Disorders; Multifactorial Inheritance; Oxytocin; Phenotype; United Kingdom

There is growing evidence to support beneficial effects of the hypothalamic synthesised hormone, oxytocin, on metabolism. However, the biological half-life of oxytocin is short and receptor activation profile unspecific.. We have characterised peptide-based oxytocin analogues with structural modifications aimed at improving half-life and receptor specificity. Following extensive in vitro and in vivo characterisation, antidiabetic efficacy of lead peptides was examined in high fat fed (HFF) mice.. Following assessment of stability against enzymatic degradation, insulin secretory activity, receptor activation profile and in vivo bioactivity, analogues 2 N (Ac-C. Novel, enzymatically stable oxytocin analogues exert beneficial antidiabetic effects in HFF mice.. These observations emphasise the, yet untapped, therapeutic potential of long-acting oxytocin-based agents for obesity and type 2 diabetes.

Topics: Animals; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Energy Intake; Female; Glucagon; Half-Life; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Male; Mice; Obesity; Oligopeptides; Oxytocin; Protein Stability; Triglycerides

Recently, it has been suggested that oxytocin (OT) has a role in metabolism and neuropsychiatry health and disease, and therefore, it may represent a potential therapeutic target. The current study aimed to investigate relationships between OT and glycemic status along with psycho-social and behavioral factors.. A total of 92 obese or overweight, African American, male subjects were enrolled in the study. Biometric and biochemical data were collected including oral glucose tolerance testing and urinary OT (measured by ELISA). Subjects also completed questionnaires on social and lifestyle factors.. OT levels were found to be significantly lower in subjects with type 2 diabetes mellitus (T2DM) compared to normal glucose tolerance (p<0.05). When stratified by OT tertiles, subjects with higher OT had lower weight, body mass index (BMI) and hemoglobin A1c, but higher eGFR which remained significant after BMI adjustment. The highest OT tertile also had more smokers and more users of psychiatric medications. A stepwise ordered logistic regression supported these findings and could account for 21% of the variation in OT categories (pseudoR2 = 0.21).. In this unique population, OT was found lower in subjects with diabetes but higher with better renal function, cigarette smoking and use of psychiatric medications. Future studies are needed to confirm these findings and examine the potential therapeutic role of OT.

Topics: Adult; Aged; Black or African American; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Glycated Hemoglobin; Humans; Male; Middle Aged; Obesity; Overweight; Oxytocin

Exact cause of the metabolic syndrome [MS], a global epidemic, is still unclear. Man has same fundamental needs to live as animals but modern man's life-style compels him to acquire certainty of resources for all his needs in a complex social network. Today money has become the sole life essential need. Contrarily none of the animals needs to earn money. Brain is also an organ of the human body with a unique thought process to define logical actions to achieve a person's goals. This way life is a flow of desires followed by logical actions. The person struggles to attain desired goals via the allostatic load but a perceived insurmountable threat can make his flow of life stalled to freeze him. Published data from varied branches of medical science indicates role of hormones in overall homeostasis. Particularly multifaceted role of serotonin is well documented. Adrenalin being the primary mediator of Cori cycle is also well known. From the integration of observations from published data with reference to common human's modern lifestyle, it is hypothesized that a perceived trapped situation in life creates acute chaos of thoughts in brain, which results in acute excess of stress hormones and concurrent depletion of resting hormones, which in turn triggers MS. In global terms, MS indicates an acute imbalance of a few hormones and implies psychosomatic roots of the disorder. This may pave a better way in deciding a personalized holistic protocol with combination of counter regulatory psychoactive medications.

Topics: Acidosis, Lactic; Allostasis; Animals; Brain; Cardiovascular Diseases; Cholecystokinin; Cholesterol; Diabetes Mellitus, Type 2; Diet; Dopamine; Epinephrine; Exercise; Homeostasis; Hormones; Humans; Hypertension; Life Style; Metabolic Syndrome; Microbiota; Models, Theoretical; Motivation; Obesity; Oxytocin; Psychophysiologic Disorders; Risk Factors; Serotonin

Oxytocin (OT) is involved in the regulation of energy metabolism and in the activation of cardioprotective mechanisms. We evaluated whether chronic treatment with OT could prevent the metabolic and cardiac abnormalities associated with diabetes and obesity using the db/db mice model. Four-week-old male db/db mice and their lean nondiabetic littermates (db/+) serving as controls were treated with OT (125 ng/kg · h) or saline vehicle for a period of 12 weeks. Compared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia, and hyperinsulinemia. These mice also exhibited a deficient cardiac OT/natriuretic system and developed systolic and diastolic dysfunction resulting from cardiomyocyte hypertrophy, fibrosis, and apoptosis. These abnormalities were associated with increased reactive oxygen species (ROS) production, inflammation, and suppressed 5'-adenosine monophosphate kinase signaling pathway. The db/db mice displayed reduced serum levels of adiponectin and adipsin and elevated resistin. OT treatment increased circulating OT levels, significantly reduced serum resistin, body fat accumulation (19%; P<.001), fasting blood glucose levels by (23%; P<.001), and improved glucose tolerance and insulin sensitivity. OT also normalized cardiac OT receptors, atrial natriuretic peptide, and brain natriuretic peptide, expressions and prevented systolic and diastolic dysfunction as well as cardiomyocyte hypertrophy, fibrosis, and apoptosis. Furthermore, OT reduced cardiac oxidative stress and inflammation and normalized the 5'-adenosine monophosphate-activated protein kinase signaling pathway. The complete normalization of cardiac structure and function by OT treatment in db/db mice contrasted with only partial improvement of hyperglycemia and hyperinsulinemia. These results indicate that chronic treatment with OT partially improves glucose and fat metabolism and reverses abnormal cardiac structural remodeling, preventing cardiac dysfunction in db/db mice.

Topics: Adiponectin; Animals; Blood Glucose; Cardiomyopathies; Diabetes Mellitus, Type 2; Energy Metabolism; Hyperinsulinism; Insulin Resistance; Male; Mice; Obesity; Oxytocin; Resistin

Oxytocin can affect energy homeostasis and has interesting potential as a metabolic disease therapeutic. We detected serum oxytocin levels in obese (OB) and type 2 diabetes mellitus (T2DM) subjects and investigated the relationships between serum oxytocin levels and glycolipid metabolism, insulin resistance, pancreatic β-cell function, and inflammation.. A total of 176 subjects were enrolled in the study, including 88 patients with newly diagnosed T2DM and 88 subjects with normal glucose tolerance (NGT). NGT and T2DM groups were divided into normal-weight (NW) and OB subgroups. We analyzed the concentrations of oxytocin by ELISA. Oral glucose tolerance testing was done, and hemoglobin A1c (HbA1c), blood lipids, and highly sensitive C-reactive protein (hs-CRP) were also measured. Insulin resistance and pancreatic β-cell function were assessed by homeostasis model assessment (HOMA).. Serum oxytocin levels were lower in the T2DM group than in the NGT group (P < .01). The levels of serum oxytocin in OB subjects were also lower than those in NW subjects (P < .01). Serum oxytocin levels were negatively correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), HbA1c, fasting plasma glucose (FPG), 2-hour plasma glucose, fasting insulin (FINS), 2-h insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), HOMA of insulin resistance (HOMA-IR), and hs-CRP and positively correlated with HOMA of β-cell function (HOMA-β) (P < .05). Multiple stepwise regression analysis showed that 2-hour plasma glucose, BMI, and TC were associated with serum oxytocin levels (P < .05). Logistic regression analyses demonstrated that serum oxytocin was significantly associated with T2DM (P < .01).. Serum oxytocin levels were decreased in T2DM as well as OB subjects.

Topics: Adiposity; Adult; Aged; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Glycolipids; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Obesity; Oxytocin; Pancreatic Function Tests

The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients.. OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments.. During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile.. The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.

Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Down-Regulation; Female; Glycated Hemoglobin; Greece; Hospitals, University; Humans; Hyperglycemia; Male; Middle Aged; Obsessive-Compulsive Disorder; Outpatient Clinics, Hospital; Oxytocin; Psychiatric Status Rating Scales; Psychotic Disorders; Somatoform Disorders

Regular physical activity is beneficial in preventing the risk of cardiovascular complications of diabetes. Recent studies showed a cardioprotective role of oxytocin (OT) to induce natriuretic peptides (NPs) and nitric oxide (NO) release. It is not known if the diabetic state is associated with a reduced OT-NPs-NO system and if exercise training improves this system. To address this, we investigated the effects of treadmill running using the db/db mouse model of type 2 diabetes. Eight-week-old db/db mice were subjected to running 5 days per week for a period of 8 weeks. The lean db/+ littermates were used as controls. Sedentary db/db mice were obese and hyperglycaemic, and exercise training was not effective in reducing body weight and the hyperglycaemic state. Compared to control mice, db/db mice had lower heart weight and heart-to-body weight ratios. In these mice, this was associated with augmented cardiac apoptosis, cardiomyocyte enlargement and collagen deposits. In addition, db/db mice displayed significant downregulation in gene expression of OT (76%), OT receptors (65%), atrial NP (ANP; 43%), brain NP (BNP; 87%) and endothelial nitric oxide synthase (eNOS) (54%) in the heart (P < 0.05). Exercise training had no effect on expression of these genes which were stimulated in control mice. In response to exercise training, the significant increment of anti-apoptotic Bcl-2 gene expression was observed only in control mice (P < 0.05). In conclusion, downregulation of the OT-NPs-NO system occurs in the heart of the young db/db mouse. Exercise training was not effective in reversing the defect, suggesting impairment of this cardiac protective system in diabetes.

Topics: Animals; Base Sequence; Cardiomyopathies; Diabetes Complications; Diabetes Mellitus, Type 2; Disease Models, Animal; DNA Primers; Down-Regulation; Genes, bcl-2; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Natriuretic Peptides; Nitric Oxide Synthase Type III; Oxytocin; Physical Conditioning, Animal; Physical Exertion; Receptors, Oxytocin; Risk Factors

The peptide hormone oxytocin plays a critical role in regulating affiliative behaviors including mating, pair-bond formation, maternal/parenting behavior, social recognition, separation distress and other aspects of attachment. Jin and colleagues recently reported intriguing findings that CD38, a transmembrane receptor with ADP-ribosyl cyclase activity, plays a critical role in maternal nurturing behavior and social recognition by regulating oxytocin secretion. This research may have implications for understanding disorders marked by deficits in social cognition and social functioning, including autism, social anxiety disorder, borderline personality disorder and schizophrenia.

Topics: ADP-ribosyl Cyclase 1; Animals; Arginine Vasopressin; Diabetes Mellitus, Type 2; Neurons; Oxytocin; Social Behavior

Local use of oxytocin-antibacterial complexes in combination with treatment of diabetes including divided insulinotherapy in patients with postinjection abscesses and non-insulin-dependent diabetes led to compensation of diabetes and earlier sanation of suppurative focus compared with patients treated by local antibiotics only.

Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chi-Square Distribution; Data Interpretation, Statistical; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Injections; Insulin; Middle Aged; Oxytocin

Eicosanoid production by intrauterine tissues from control and neonatal-streptozotocin induced diabetic rats during late pregnancy was evaluated. In diabetic placenta the release of 6-keto-PGF1alpha was found diminished when compared to controls. In addition, LTB4 generation was increased in diabetic placenta. No alterations in the production of TXA2, PGE2, PGE1 and PGF2alpha was found when diabetic and control placenta were compared. In amnion tissue a decreased generation of 6-keto-PGF1alpha was observed in the diabetic group, but no alteration in any other eicosanoid evaluated was found. Oxytocin (5 mU/ml, in vitro), which increases prostaglandin synthesis in rabbit and human amnion tissues, did not modify eicosanoid generation in control rat amnion. In contrast, in diabetic amnion the presence of oxytocin further decreased the release of 6-keto-PGF1alpha and diminished PGE1 generation. The present results suggest that this mildly diabetic state induces alterations in eicosanoid production in intrauterine tissues, abnormalities probably enhanced during parturition, when endogenous concentrations of oxytocin are elevated.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Amnion; Animals; Culture Media; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dinoprost; Dinoprostone; Eicosanoids; Female; Humans; In Vitro Techniques; Oxytocin; Placenta; Pregnancy; Pregnancy in Diabetics; Rabbits; Rats; Rats, Wistar; Thromboxane A2

Eicosanoid production, glucose (Glu), glycogen (Gly) and triglyceride (TG) metabolism, spontaneous contractile activity, PGF2 alpha and oxytocin-induced contractions have been studied in uterine tissue obtained from control (C) and non-insulin-dependent diabetic (D) rats prior to parturition. Parturition occurs on day 22 of gestation in control animals, whereas a 24 hr delay was observed in diabetic rats. Production of PGE2, PGE1, 6-keto-PGF1 alpha, PGF2 alpha, TXB2 and LTB4 was similar in uterine tissue obtained from control and diabetic rats on day 21 of pregnancy. Uterine metabolism, on day 21 of pregnancy, based on the production of 14CO2 from U14C-glucose was lower in tissues obtained from diabetic rats than in controls. Levels of TG were similar at 0 hr and after 60 min incubation in Glu or Glu-free medium in both experimental groups. Initially Gly levels in diabetic and control uteri were similar. After 60 minutes of incubation, levels of Gly in control tissue decreased only in the absence of Glu in the incubation medium. In contrast, in diabetic uterine strips, levels of Gly decreased after 60 minutes of incubation either in Glu or Glu-free medium. "In vitro" isometric-developed tension (IDT) evaluated on day 21 (C and D) and 22 (D) of pregnancy was similar at 0 hr in control and diabetic uterine preparations, but IDT in both diabetic groups was decreased after a 40 minute incubation when compared to controls. Alterations in PGF2 alpha-induced uterine responses were not seen in 21 or 22 days pregnant diabetic uterine tissue when compared to controls. In contrast, impaired oxytocin responses were observed in diabetic uteri on day 21 of gestation, but they were similar to control responses of uterine tissue from day 22 diabetic rats. We conclude that in the non-insulin-dependent late pregnant rat, there are no alterations in uterine tissue eicosanoid production, but metabolic and contractile abnormalities are present. Involvement of these alterations in the delayed initiation of parturition is discussed.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dinoprost; Dose-Response Relationship, Drug; Eicosanoids; Female; Glucose; Glycogen; In Vitro Techniques; Isometric Contraction; Oxytocin; Pregnancy; Rats; Rats, Wistar; Streptozocin; Time Factors; Triglycerides; Uterine Contraction; Uterus

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Islets of Langerhans; Male; Oxytocin; Rats; Rats, Inbred Strains