oxytocin and Prediabetic-State

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

A comparison has been made between the effectiveness of infusing prostaglandin E(2) with Syntocinon for the induction of labour in the presence of intact membranes. Rapid titration schedules were used to induce an early uterine response. All 15 subjects receiving prostaglandin E(2) achieved cervical dilatation, whereas this occurred in only 9 out of 15 patients receiving Syntocinon.

Topics: Adult; Apgar Score; Cervix Uteri; Dilatation; Extraembryonic Membranes; Female; Humans; Hypertension; Injections, Intravenous; Labor, Induced; Oxytocin; Pre-Eclampsia; Prediabetic State; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Pregnancy, Prolonged; Prostaglandins

The aim of this study was to explore the differences in OXT levels in metabolic syndrome (MetS) subjects, newly diagnosed type 2 diabetes mellitus (T2D), and prediabetes subjects vs. MetS subjects without glucose intolerance (non-diabetic MetS). It was also intended to determine the relationship between plasma OXT levels and inflammatory markers in those subjects.. Along with 45 lean and normoglycemic controls, a total of 190 MetS subjects (61 men, 129 women) were enrolled. Colorimetric enzymatic assays of the following components were performed: plasma OXT, high-sensitivity C-reactive protein (hs-CRP), macrophage chemoattractant protein 1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), matrix metalloproteinase 9 (MMP-9), resistin, adiponectin, leptin, macrophage migration inhibitory factor (MIF), tumor necrosis factor α (TNF-α), thrompospondin 1 (TSP-1), interleukin 10 (IL-10), interleukin 6 (IL-6), and glucagon.. hsCRP, PAI-1, resistin, leptin-to-adiponection-ratio (LAR), TNF-α, TSP-1, and MIF were significantly higher in both MetS groups (prediabetic and T2DM) than in MetS-only subjects. Leptin and MMP-9 were significantly higher in the MetS-T2DM group (but not in MetS-prediabetics) vs. MetS-only subjects. Conversely adiponectin, OXT, MCP-1, and IL-10 were significantly lower in both MetS groups (prediabetic and T2DM) than in MetS-only subjects. There was no marked discrepancy in either glucagon or IL-6 levels among the three MetS groups. In the entire MetS study population, OXT correlated substantially and proportionally with MCP-1, IL-10, and IL-6; it correlated negatively with HbA1c, fasting plasma glucose (FPG), PAI-1, MMP-9, TNF-α, TSP-1, resistin, adiponectin, leptin, LAR, and MIF. No association could be observed between OXT and glucagon.. OXT may be a substantial surrogate predictive/prognostic tool and putative pharmacotherapeutic target in metabolic anomalies and related disorders.

Topics: Adult; Biomarkers; Female; Glucose Intolerance; Humans; Inflammation; Inflammation Mediators; Male; Metabolic Syndrome; Middle Aged; Oxytocin; Prediabetic State