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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of endogenous insulin on the secretion of immunoreactive gastric inhibitory polypeptide (IR-GIP) the response of IR-GIP and immunoreactive insulin (IRI) to an oral fat load (100 g triglyceride) alone and during an intravenous glucose infusion (0.7 g/kg/h) was examined in normal weight and obese subjects. In normal weight subjects the fat induced integrated rise of IR-GIP was 112.7 +/- 9.4 ng/ml/120 min. When glucose and fat were given together this IR-GIP response was lowered to 46.2 +/- 2.9 ng/ml/120 min while the serum IRI response to i.v. glucose and the glucose tolerance were enhanced by fat ingestion. In obese subjects with normal glucose tolerance the GIP suppressing effect of i.v. glucose infusion was less marked than in controls. The integrated IR-GIP response to fat ingestion was 225.6 +/- 20.3 mg/ml/120 min and to fat plus glucose 152.6 +/- 14.8 ng/ml/120 min. In obese subjects with glucose intolerance i.v. glucose completely failed to lower the exaggerated secretion of IR-GIP following oral fat. Thus, a graded abnormality of the GIP response to glucose induced insulin release occurs in obesity with normal and pathological glucose tolerance. After reducing the ideal body weight of six obese subjects with glucose intolerance by hypocaloric diet for 3 weeks the exaggerated rise of IR-GIP after oral fat was reversed and the lowering effect of i.v. glucose on the IR-GIP response re-established.
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PMID:Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance. 11 43

The 'fatty' Zucker and more recently the JCR:LA-cp 'corpulent' have been studied extensively as genetic models of the hyperinsulinemia, insulin resistance and abnormal fat metabolism of obesity. It has been hypothesized that an abnormal enteroinsular axis leading to hypersecretion of the insulin releasing hormone gastric inhibitory polypeptide (GIP) could contribute to the hyperinsulinemia of obesity, although this has been controversial. The present study was undertaken to compare the enteroinsular axis in fatty Zucker and JCR:LA-cp rats. The in vivo GIP and insulin responses to an oral glucose challenge, as well as glucose tolerance, were compared in lean and obese phenotypes of both strains as well as the sensitivity of the perfused pancreas to the secretagogues glucose, arginine and GIP. In addition, the effect of perfusate glucose concentration on the beta cell response to GIP was assessed in both strains. Tissue samples from the pancreas were taken for immunocytochemical analysis of comparative size and composition of pancreatic islets. Our results indicate that corpulent rats are hyperGIPemic when compared to fatty Zuckers and that hyperinsulinemia (both in vivo and in vitro) is more severe in the JCR:LA-cp than in the fatty Zucker, as is the degree of insulin resistance (as evidenced by glucose intolerance). Islets of corpulent rats were found to be larger than those of fa/fa rats as well as having a larger area occupied by beta cells. It was concluded that GIP may contribute to fasting hyperinsulinemia in the Zucker rat (as a result of a defective glucose threshold for the insulinotropic action of GIP), whereas the hyperGIPemia of the JCR:LA-cp rat may contribute to the massive nutrient-stimulated hyperinsulinemia observed in the male phenotype of this strain.
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PMID:Comparison of the enteroinsular axis in two strains of obese rat, the fatty Zucker and the JCR:LA-corpulent. 189 23

The effect of dietary sucrose and fat in the form of coconut fat (rich in saturated fatty acids) or safflowerseed oil (rich in polyunsaturated fatty acids) was examined on the development of obesity and impaired glucose homeostasis in ob/ob mice. Isoenergetic high sucrose or high fat diets were fed to ob/ob mice from 3-11 weeks of age. Energy intake of mice fed diets rich in fat were similar, and exceeded that attained with the sucrose diet. Body weight gain was greatest in the sucrose-fed mice and least in those fed safflowerseed oil. With the exception of insulin sensitivity which was enhanced with safflowerseed oil, plasma concentrations of glucose and gastric inhibitory polypeptide (GIP), glucose tolerance, intestinal GIP content and the GIP response to oral fat were similar. However, mice fed the high sucrose diet exhibited markedly elevated plasma insulin concentrations and an enhanced pancreatic insulin content. Since the hyperinsulinaemic action of sucrose cannot be attributed to elevated GIP or glucose concentrations, the involvement of other insulin-releasing hormones released from the intestine by sucrose is suggested. The results indicate that the relative amounts of carbohydrate and fat in the diet have an important modulating effect on the development of the ob/ob syndrome. The type of fatty acids in the diet does not appear to be a particularly important determinant for expression of the ob gene.
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PMID:Effects of diets rich in sucrose, coconut fat and safflowerseed oil on the development of the obese hyperglycaemic (ob/ob) syndrome in mice. 209 92

In previous studies we found that in healthy subjects, 5 and 10 g of a partially purified amylase inhibitor delayed and decreased starch digestion and reduced postprandial plasma glucose after a starch meal but produced diarrhea in two of six and four of six subjects, respectively. Thus, we wondered whether lower doses of the inhibitor, when given with a meal that contained protein and fat as well as carbohydrate, would have the same effect on carbohydrate tolerance without causing diarrhea. Eight healthy subjects were randomized to receive 2.0 or 2.9 g of the inhibitor with a 650-calorie meal that contained carbohydrate, fat, and protein. In comparison with a placebo, ingestion of 2.9 g, but not 2.0 g, of the inhibitor significantly reduced postprandial increases in plasma glucose (P less than 0.05), C peptide (P less than 0.03), and gastric inhibitory polypeptide (P less than 0.008). Similarly, 2.9 g of the inhibitor in comparison with 2.0 g was associated with more carbohydrate malabsorption and more breath hydrogen excretion. Because the carbohydrate malabsorption observed with the 2.9-g dose was similar to that with the previously tested 5- and 10-g doses of the inhibitor but diarrhea was less frequent, impurities in the partially purified preparation may, in part, have been responsible for these adverse effects. We conclude that 2.9 g of the amylase inhibitor given with a meal that contains a mixture of nutrients is effective in increasing carbohydrate tolerance without causing diarrhea. Therefore, this dose is appropriate for use in studies to determine whether the inhibitor has a beneficial effect in patients with diabetes mellitus or obesity.
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PMID:Effect of a purified amylase inhibitor on carbohydrate metabolism after a mixed meal in healthy humans. 243 11

The response of immunoreactive gastric inhibitory polypeptide (IR-GIP), immunoreactive insulin (IRI) and immunoreactive C-peptide (IR-C-peptide) to the ingestion of mixed liquid test meals containing 1031 kcal (550 ml) and 422 kcal was studied in 17 obese and 17 normal weight control subjects. When the 422 kcal load was ingested in a volume of 550 ml, the plasma IR-GIP response was significantly greater than in a volume of 225 ml at 15 and 30 min in lean and obese subjects, but the total integrated IR-GIP response was not significantly different between the obese and lean group. Also intraduodenal infusion of 150 ml (280 kcal) of the test meal elicited identical plasma IR-GIP concentrations in lean and obese subjects. An exaggerated IR-GIP response in obese subjects was seen only following the 1031 kcal load (integrated IR-GIP response: 23.6 +/- 1.9 in lean subjects vs 50.3 +/- 3.8 nmol/l/180 min in obese subjects; p less than 0.01). The IRI response was always significantly greater in obese than in lean subjects and not related to the GIP response. Fasting plasma IR-C-peptide levels were significantly elevated in obese subjects (lean: 0.52 +/- 0.04; obese: 1.42 +/- 0.12 nmol/l; p less than 0.005), but the postprandial integrated IR-C-peptide responses in the obese and lean group were identical, indicating decreased hepatic insulin extraction in obesity. It is concluded that an exaggerated IR-GIP response in obesity occurs only after ingestion of a high calorie meal probably as consequence of an increased gastric emptying rate and that the hyperinsulinemic response of obese subjects is not attributable to GIP hypersecretion.
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PMID:Gastric inhibitory polypeptide (GIP) hypersecretion in obesity depends on meal size and is not related to hyperinsulinemia. 266 6

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), has been isolated and characterized because of its enterogastrone-type effects. It is also named glucose-dependent insulinotropic polypeptide and is actually considered to be the main incretin factor of the entero-insular axis. Besides these well-described effects on gastric secretion and pancreatic beta cells, it also has direct metabolic effects on other tissues and organs, such as adipose tissue, liver, muscle, gastrointestinal tract and brain. In adipose tissue it is involved in the activation and regulation of lipoprotein lipase (LPL); it also inhibits glucagon-induced lipolysis and potentiates the effect of insulin on incorporation of fatty acids into triglycerides. It may play a role in the development of obesity because of the hypersensitivity of adipose tissue of obese animals to some of these actions. In the liver it does not modify insulin extraction, and its incretin effects are due only to the stimulation of insulin secretion and synthesis. It reduces hepatic glucose output and inhibits glucagon-stimulated glycogenolysis. It might increase glucose utilization in peripheral tissues such as muscle. GIP also has an effect on the volume and/or electrolyte composition of intestinal secretion and saliva. The functional importance of its effect on the hormones of the anterior pituitary lobe remains to be established, as it has never been detected in the brain. Its links with insulin are very close and the presence of insulin is sometimes necessary for the greater efficiency of both hormones. GIP can be considered as a true metabolic hormone, with most of its functions tending to increase anabolism.
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PMID:Gastric inhibitory polypeptide: a gut hormone with anabolic functions. 266 79

Pancreatic islet peptides, as well as other gastrointestinal hormones, have been implicated in both the pathogenesis of obesity and the etiology of associated metabolic derangements. This study evaluated the pancreatic islet and gastrointestinal (GI) hormone response to oral glucose in 20 morbidly obese (151% above ideal body weight) patients. Glucose intolerance, hyperinsulinism, and exaggerated gastric inhibitory polypeptide (GIP) release occurred following glucose ingestion. Significant release of PP occurred in 14 patients, while only six patients had release of somatostatin. No significant changes in plasma concentrations of glucagon occurred. Since GIP is insulinotropic in the presence of hyperglycemia, the hyperinsulinism of morbid obesity may be secondary to the abnormally high glucose-stimulated GIP levels in these patients. Failure of glucagon suppression in response to oral glucose many contribute to the hyperglycemia noted. Somatostatin and pancreatic polypeptide may be responsible for some of the metabolic derangements of morbid obesity.
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PMID:Pancreatic islet hormone response to oral glucose in morbidly obese patients. 286 Aug 76

The effects of gastric inhibitory polypeptide (GIP) on glucose and lipid metabolism of isolated rat adipocytes were investigated. In a dose-dependent manner, GIP stimulated 2-deoxy-glucose uptake increasing the glucose transport rate by up to 140% at a concentration of 10(-7) mol/l. GIP also stimulated the conversion of 14C-glucose into extractable lipids by up to 81% at 10(-7) mol/l. Insulin-stimulated 2-deoxy-glucose uptake and lipogenesis were additively enhanced by the presence of GIP. Insulin binding was slightly but not significantly increased by addition of GIP, mainly due to an increase in receptor affinity. GIP had a weak lipolytic activity, but lipolysis elicited by glucagon or isoproterenol was potently reduced. In conclusion, independent of its insulinotropic action, GIP showed a insulin-like activity on glucose metabolism and lipolysis in rat adipose tissue. The possible role of GIP for the development of obesity is discussed.
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PMID:Effects of gastric inhibitory polypeptide on glucose and lipid metabolism of isolated rat adipocytes. 307 52

To assess the contribution of gastric inhibitory polypeptide (GIP) to the postprandial hyperinsulinemia of obesity, secretion rates of GIP (generated from kinetic analyses from infusions of porcine GIP) and insulin (from C-peptide applied to a validated kinetic model) to meals of 3 sizes were determined in 10 obese (5 male and 5 female) and 10 lean, sex- and age-matched healthy subjects. Although the postprandial secretion rates of GIP were greater in obese subjects (P = 0.03), postprandial concentrations of GIP were not. The latter may be explained by the greater volume of distribution of GIP in obese subjects (P = 0.036). Secretion rates and volume of distribution of GIP were correlated (r = 0.652, P less than 0.01). Despite excessive integrated postprandial (P = 0.010) insulin concentrations, insulin secretion was not significantly different between obese and lean subjects. We conclude that 1) although postprandial plasma GIP concentrations are normal, GIP secretion is increased in obesity, 2) the postprandial hyperinsulinemia of obesity is not due to excessive insulin secretion but is likely secondary to altered insulin clearance, and 3) GIP cannot account for the hyperinsulinemia of obesity through its insulinotropic action.
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PMID:Role of gastric inhibitory polypeptide in postprandial hyperinsulinemia of obesity. 328 53

Diabetes, the most common metabolic disease, is responsible for the deaths of over 300,000 Americans annually. The incidence of the disease increases with age and since the U.S. population is graying, prevalence is also increasing. Obesity and family history are strong predictors of diabetes. The etiology of Type II diabetes is heterogeneous. The hyperglycemia of Type II diabetes can result from a variety of metabolic defects including impaired beta cell secretion, receptor deficiencies, or abnormal hepatic production or uptake of glucose. Other glucoregulatory hormones such as glucagon, growth hormone, cortisol, thyroid hormones, somatostatin, and gastric inhibitory polypeptide may contribute to the aberrations of carbohydrate metabolism. Environmental factors including stress, diet, and exercise may also contribute to the disease. Since most diabetics are obese, weight loss should be the first priority in improving status. A variety of diet and exercise regimens may help achieve this goal or even improve glucose control without weight loss. Due to the heterogeneity of the disease individualized treatment must be used to improve status of patients with the various metabolic defects of Type II diabetes.
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PMID:Dietary sugars and carbohydrate metabolism in type II diabetes. 330 10


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