peptide-yy and Hyperglycemia

Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial, glucose, insulin, PYY3-36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h) of PYY3-36 were lower (meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05), whereas insulin (meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and ghrelin (meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0-0.5, 4-4.5, and 8-8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P < 0.05). Also, meal-induced fullness was prevented (meal 1, P = 0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia. Furthermore, trends in ghrelin, PYY3-36, and fullness were described by different polynomial functions between the trials. In conclusion, hyperglycemia abolishes meal-induced satiety and dysregulates postprandial responses of the gut hormones PYY3-36 and ghrelin in overweight/obese healthy humans.

Topics: Blood Glucose; Eating; Female; Ghrelin; Health; Humans; Hyperglycemia; Insulin; Male; Meals; Middle Aged; Obesity; Overweight; Peptide Fragments; Peptide YY; Satiety Response

Fat is the most potent stimulus for glucagon-like peptide-1 (GLP-1) secretion. The aims of this study were to determine whether dipeptidyl peptidase IV (DPP-IV) inhibition would enhance plasma active incretin [glucose-dependent insulinotropic polypeptide (GIP), GLP-1] concentrations and modulate the glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to intraduodenal fat infusion. In a double-blind, randomized, placebo-controlled crossover design, 16 healthy lean males received 50 mg vildagliptin (V), or matched placebo (P), before intraduodenal fat infusion (2 kcal/min, 120 min). Blood glucose, plasma insulin, glucagon, active GLP-1, and GIP and peptide YY (PYY)-(3-36) concentrations; resting energy expenditure; and energy intake at a subsequent buffet meal (time = 120-150 min) were quantified. Data are presented as areas under the curve (0-120 min, means ± SE). Vildagliptin decreased glycemia (P: 598 ± 8 vs. V: 573 ± 9 mmol·l⁻¹·min⁻¹, P < 0.05) during intraduodenal lipid. This was associated with increased insulin (P: 15,964 ± 1,193 vs. V: 18,243 ± 1,257 pmol·l⁻¹·min⁻¹, P < 0.05), reduced glucagon (P: 1,008 ± 52 vs. V: 902 ± 46 pmol·l⁻¹·min⁻¹, P < 0.05), enhanced active GLP-1 (P: 294 ± 40 vs. V: 694 ± 78 pmol·l⁻¹·min⁻¹) and GIP (P: 2,748 ± 77 vs. V: 4,256 ± 157 pmol·l⁻¹·min⁻¹), and reduced PYY-(3-36) (P: 9,527 ± 754 vs. V: 4,469 ± 431 pM/min) concentrations compared with placebo (P < 0.05, for all). Vildagliptin increased resting energy expenditure (P: 1,821 ± 54 vs. V: 1,896 ± 65 kcal/day, P < 0.05) without effecting energy intake. Vildagliptin 1) modulates the effects of intraduodenal fat to enhance active GLP-1 and GIP, stimulate insulin, and suppress glucagon, thereby reducing glycemia and 2) increases energy expenditure. These observations suggest that the fat content of a meal, by enhancing GLP-1 and GIP secretion, may contribute to the response to DPP-IV inhibition.

Topics: Adamantane; Adolescent; Adult; Appetite Regulation; Cross-Over Studies; Dietary Fats; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Energy Intake; Energy Metabolism; Food-Drug Interactions; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Middle Aged; Nitriles; Peptide Fragments; Peptide YY; Postprandial Period; Pyrrolidines; Vildagliptin; Young Adult

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

Prader-Willi syndrome (PWS) is characterized by life-threatening childhood-onset hyperphagia, obesity and, uniquely, high plasma levels of ghrelin, the orexigenic gastric hormone. Somatostatin suppresses ghrelin secretion in normal subjects. We therefore examined the effect of somatostatin on plasma ghrelin and appetite in four male PWS adults fasted overnight in a double-blind, placebo-controlled, randomized cross-over study. Subjects received an intravenous infusion of somatostatin (250 microg/hr) or saline for 300 min, and had blood samples taken every 30 min for measurement of plasma ghrelin and PYY3-36 (anorexigenic intestinal hormone) by radio-immunoassay, and glucose. Appetite was measured by counting sandwiches eaten over a 60 min free food access period from +120 min. Despite somatostatin lowering fasting plasma ghrelin by 60 +/- 2% (P = 0.04) to levels seen in non-PWS men, there was no associated reduction in food intake (105 +/- 9% of food intake during saline infusion, P = 0.6). Somatostatin also lowered plasma PYY levels by 45 +/- 16% (P = 0.04), and produced post-prandial hyperglycemia (P = 0.04). We conclude that either hyperghrelinemia may not contribute to hyperphagia in PWS adults, or perhaps concomitant reductions in anorexigenic gastrointestinal hormones by somatostatin counteracted any anorexigenic effect of lowering orexigenic ghrelin. Somatostatin analogues may therefore not be an effective therapy for obesity in PWS. Larger chronic studies with long-acting somatostatin analogues will be needed to determine their benefits and risks in treating PWS obesity.

Topics: Adult; Appetite; Blood Glucose; Cross-Over Studies; Double-Blind Method; Eating; Ghrelin; Hormones; Humans; Hyperglycemia; Infusions, Intravenous; Male; Peptide Fragments; Peptide Hormones; Peptide YY; Postprandial Period; Prader-Willi Syndrome; Somatostatin

Pro-inflammatory cytokines, such as interleukin (IL)-6, tumour necrosis factor (TNF)α, and monocyte chemoattractant protein (MCP)-1, are often elevated in individuals after acute pancreatitis but what determines their levels is poorly understood. Gut hormones have emerged as possible modulators of inflammatory response. The aim was to investigate the associations between pro-inflammatory cytokines and a comprehensive panel of gut hormones after an episode of acute pancreatitis.. Fasting blood samples were collected to measure cytokines (IL-6, TNFα, and MCP-1) and gut hormones (cholecystokinin, gastric inhibitory peptide (GIP), ghrelin, glicentin, glucagon-like peptide-1, oxyntomodulin, peptide YY, secretin, and vasoactive intestinal peptide). A series of linear regression analyses was conducted and four statistical models were used to adjust for patient- and pancreatitis-related covariates.. A total of 83 individuals were recruited. GIP and peptide YY were significantly (p < 0.001) associated with IL-6, TNFα, MCP-1, consistently in all the four models. Every 1 ng/mL change in GIP resulted in a 16.2, 3.2, and 50.8% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. Every 1 ng/mL change in peptide YY resulted in a 7.0, 2.4, and 32.1% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. GIP independently contributed 29.0-36.5% and peptide YY - 17.4-48.9% to circulating levels of the studied pro-inflammatory cytokines. The other seven studied gut hormones did not show consistently significant associations with pro-inflammatory cytokines.. GIP and peptide YY appear to be involved in perpetuation of subclinical inflammation following an episode of acute pancreatitis, which is known to play an important role in the pathogenesis of blood glucose derangements. These findings advance the understanding of mechanisms underlying diabetes of the exocrine pancreas and have translational implications.

Topics: Acute Disease; Adult; Aged; Chemokine CCL2; Cross-Sectional Studies; Fasting; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Humans; Hyperglycemia; Interleukin-6; Male; Middle Aged; Pancreatitis; Peptide YY; Pregnancy; Tumor Necrosis Factor-alpha

In the pancreas, peptide YY (PYY) is expressed by a subpopulation of nonbeta cells in the islets of Langerhans. We investigated the function of these cells in the pancreas of adult mice.. We generated mice in which administration of diphtheria toxin (DT) led to specific ablation of PYY-expressing cells. We investigated the effects of loss of PYY cells on glucose homeostasis.. Loss of PYY cells in adult mice resulted in severe hyperglycemia, which was associated with significant loss of pancreatic insulin and disruption of islet morphology. In vitro administration of DT to isolated islets significantly reduced numbers of PYY-expressing cells and levels of insulin. Administration of either pancreatic polypeptide (a strong agonist of the receptor Y(4)) or PYY(3-36) (a selective agonist of the receptor Y(2)) did not restore loss of pancreatic insulin following administration of DT. However, a long-acting PYY analogue reduced the loss of insulin, and administration of this analogue reduced the hyperglycemia and insulin loss induced by streptozotocin in mice.. PYY appears to regulate beta cell function and survival via the receptor Y(1/2). These findings might be developed to treat and prevent loss of beta cells in patients with diabetes mellitus.

Topics: Animals; Biomarkers; Cell Death; Cell Survival; Diphtheria Toxin; Hyperglycemia; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pancreatic Polypeptide; Peptide Fragments; Peptide YY

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

This study examined the relationship between islet neurohormonal characteristics and the defective glucose-stimulated insulin secretion in genetic type 2 diabetic Chinese hamsters. Two different sublines were studied: diabetes-prone CHIG hamsters and control CHIA hamsters. The CHIG hamsters were divided into three subgroups, depending on severity of hyperglycemia. Compared to normoglycemic CHIG hamsters and control CHIA hamsters, severely hyperglycemic CHIG hamsters (glucose > 15 mmol/l) showed marked glucose intolerance during i.p. glucose tolerance test and 75% impairment of glucose-stimulated insulin secretion from isolated islets. Mildly hyperglycemic CHIG animals (glucose 7.2-15 mmol/l) showed only moderate glucose intolerance and a 60% impairment of glucose-stimulated insulin secretion from the islets. Immunostaining for neuropeptide Y and tyrosine hydroxylase (markers for adrenergic nerves) and for vasoactive intestinal peptide (marker for cholinergic nerves) revealed significant reduction in immunostaining of islets in the severely but not in the mildly hyperglycemic animals, compared to control CHIA hamsters. The study therefore provides evidence that in this model of type 2 diabetes in Chinese hamsters, severe hyperglycemia is accompanied not only by marked glucose intolerance and islet dysfunction but also by reduced islet innervation. This suggests that islet neuronal alterations may contribute to islet dysfunction in severe but not in mild diabetes.

Topics: Animals; Animals, Inbred Strains; Blood Glucose; Cricetinae; Cricetulus; Diabetes Mellitus, Type 2; Female; Glucose; Glucose Intolerance; Glucose Tolerance Test; Hyperglycemia; Immunohistochemistry; Insulin; Insulin Secretion; Islets of Langerhans; Male; Nerve Fibers; Neuropeptides; Pancreas; Pancreatic Hormones; Peptide YY