peptide-yy and Hyperinsulinism

Obesity is strongly associated with hypertension and cardiovascular disease. Several central and peripheral abnormalities that can explain the development or maintenance of high arterial pressure in obesity have been identified. These include activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Obesity is also associated with endothelial dysfunction and renal functional abnormalities that may play a role in the development of hypertension. The continuing discovery of mechanisms regulating appetite and metabolism is likely to lead to new therapies for obesity-induced hypertension. Better understanding of leptin signaling in the hypothalamus and the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. Other hunger and satiety signals such as ghrelin and peptide YY are potentially attractive therapeutic strategies for treatment of obesity and its complications. These recent discoveries should lead to novel strategies for treatment of obesity and hypertension.

Topics: Adiponectin; Aldosterone; Animals; Appetite; Endothelium, Vascular; Energy Metabolism; Ghrelin; Humans; Hyperinsulinism; Hypertension; Intercellular Signaling Peptides and Proteins; Kidney; Leptin; Mice; Mice, Mutant Strains; Mineralocorticoid Receptor Antagonists; Obesity; Peptide Hormones; Peptide YY; Receptors, Cell Surface; Receptors, Leptin; Renin-Angiotensin System; Repressor Proteins; Satiation; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Sympathetic Nervous System; Transcription Factors

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

The aim of this study was to investigate the appetite hormones and metabolic responses of hyperinsulinemic subjects to high-protein (HP) meals as compared to high-carbohydrate (HC) and high-fat (HF) meals.. Fifteen hyperinsulinemic normoglycemic men received, on 3 separate occasions, HP, HC, or HF meals in a randomized crossover design. Blood samples were collected before and after the ingestion of each meal. Postprandially, acylated ghrelin, PYY(3-36), insulin, glucose, and triglycerides were measured.. While the HC meal induced an acutely greater postprandial ghrelin decrease below baseline, the HP meal maintained this decline significantly more than the HF meal at 240 min. Postprandial PYY(3-36) responses did not significantly vary with time and meal composition. Postprandial insulin and glucose peaks were significantly lower following the HP and HF meals in comparison to the HC meal, whereas triglyceride responses were significantly higher following the HF meal. Significant correlations, negative between acylated ghrelin and insulin and positive between PYY(3-36) and insulin, were observed.. In hyperinsulinemic normoglycemic men, HP meals ensure a longer-lasting suppression of circulating ghrelin levels and result in more favorable metabolic responses, characterized by a lower surge of postprandial insulin and glucose and a reduced postprandial triglyceride response, as compared to both HC and HF meals.

Topics: Adolescent; Adult; Appetite Regulation; Blood Glucose; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Ghrelin; Humans; Hyperinsulinism; Insulin; Male; Obesity; Peptide YY; Postprandial Period; Triglycerides; Young Adult

Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis.. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet.. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy (-/-) mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo-pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity.. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding.

Topics: Adipose Tissue; Animals; Body Weight; Chromosomes, Artificial, Bacterial; Cloning, Molecular; DNA Primers; Energy Intake; Female; Glucose Tolerance Test; Hyperinsulinism; Male; Mice; Mice, Knockout; Obesity; Organ Size; Peptide YY; Polymerase Chain Reaction; Restriction Mapping; Sex Characteristics

Peptide YY(3-36) (PYY(3-36)) is released by the gut in response to nutrient ingestion. It modulates the activities of orexigenic neuropeptide Y (NPY) neurons and anorexigenic proopiomelanocortin (POMC) neurons in the hypothalamus to inhibit food intake. Because both NPY and POMC have also been shown to impact insulin action, we wondered whether PYY(3-36) could improve insulin sensitivity. To address this question, we examined the acute effect of intravenous PYY(3-36) on glucose and free fatty acid (FFA) flux during a hyperinsulinemic-euglycemic clamp in mice maintained on a high-fat diet for 2 weeks before the experiment. We also evaluated the effects of PYY(3-36) infusion on glucose uptake in muscle and adipose tissue in this experimental context. Under basal conditions, none of the metabolic parameters were affected by PYY(3-36). Under hyperinsulinemic conditions, glucose disposal was significantly increased in PYY(3-36)-infused compared with vehicle-infused mice (103.8 +/- 10.9 vs. 76.1 +/- 11.4 micromol.min(-1).kg(-1), respectively; P = 0.001). Accordingly, glucose uptake in muscle and adipose tissue was greater in PYY(3-36)-treated animals, although the difference with controls did not reach statistical significance in adipose tissue (muscle: 2.1 +/- 0.5 vs. 1.5 +/- 0.5 micromol/g tissue, P = 0.049; adipose tissue: 0.8 +/- 0.4 vs. 0.4 +/- 0.3 micromol/g tissue, P = 0.08). In contrast, PYY(3-36) did not impact insulin action on endogenous glucose production or FFA metabolism. These data indicate that PYY(3-36) reinforces insulin action on glucose disposal in mice fed a high-fat diet, through a mechanism that is independent of food intake and body weight. In contrast, it leaves glucose production and lipid flux largely unaffected in this experimental context.

Topics: Adipose Tissue; Animals; Biological Transport; Blood Glucose; Dietary Fats; Fasting; Fatty Acids, Nonesterified; Glucose; Glucose Clamp Technique; Hyperinsulinism; Injections, Intravenous; Insulin; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Peptide Fragments; Peptide YY