Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric inhibitory polypeptide (GIP) is released from the duodenum and jejunum following the ingestion of glucose, fat and amino acids. This hormone potentiates the glucose-induced insulin release from the beta-cells of the pancreas. The role of GIP as "incretin" is discussed. The method of the radioimmunoassay for the determination of GIP in serum samples is described. The lower limit of sensitivity of the GIP radioimmunoassay is in the range of 30-50 pg per ml serum. The described radioimmunoassay is sensitive enough to determine fasting levels of GIP in normal subjects (287 +/- 59 pg/ml). The clinical and pathophysiological importance of GIP is discussed by means of various diseases (obesity, maturity-onset diabetes mellitus, duodenal ulcer disease).
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PMID:[Gastric inhibitory polypeptide (GIP) (author's transl]. 65 87

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

Studies were carried out in 32 obese patients and 30 normal-weight control subjects to ascertain the response of glucose-dependent insulinotropic polypeptide (GIP) and insulin to (1) oral and intravenous glucose (10 obese and 10 control subjects), (2) oral fat and intravenous glucose (eight obese and six control subjects) and (3) mixed test meal (14 obese and 14 control subjects). Basal mean insulin was higher in the obese (99 pmol/l) than in the control group (40 pmol/l), but fasting blood glucose and GIP were not significantly different from normal. The total integrated response of insulin in obese subjects after oral glucose was 54.1 versus 33.3 nmol . l-1 . h-1 in control subjects; glucose and GIP responses were similar in both groups. After intravenous glucose the integrated insulin response was 8.8 in the obese versus 5.0 nmol . l-1 . h-1 in control subjects; GIP was unaffected by intravenous glucose and glucose levels were similar. Following oral fat and intravenous glucose, insulin secretion was again abnormal in the obese, 24.5 versus 7.3 nmol . l-1 . h-1 in controls, but GIP responses were normal. However, the control subjects became hypoglycaemic after this test: blood glucose 2.8 mmol/l at 150 min compared with 4.6 mmol/l in the obese group. The insulin response to a mixed meal was also abnormal in obesity.
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PMID:Disparity between glucose-dependent insulinotropic polypeptide and insulin responses in obese man. 636 Jul 77

The involvement of the gut hormone GIP (gastric inhibitory polypeptide, glucose-dependent insulinotropic polypeptide) in the hyperinsulinemia of the adult obese Zucker rat was investigated. Glucose, insulin, and GIP responses to oral glucose were compared in lean and obese rats. The sensitivity of the isolated, perfused pancreas to glucose and GIP was studied in basal and hyperglycemic conditions in lean and obese rats. Immunocytochemical studies of the gut and pancreas were also carried out. The glucose and GIP responses to oral glucose were similar in lean and obese rats, but obese animals were hyperinsulinemic compared with lean controls under fasting conditions and after oral glucose. The isolated, perfused pancreas of obese Zucker rats had an elevated insulin response to 300 mg/dl glucose. GIP increased the insulin response to 300 mg/dl glucose threefold in both lean and obese rats. At basal glucose levels (80 mg/dl), GIP augmented insulin release in obese but not in lean rats. Immunocytochemical studies demonstrated the presence of enlarged islets in obese rats due to an increase in the B-cell mass. A-, D-, and PP-cells appeared normal. Obese and lean rats had similar numbers of GIP-containing cells in the gut. This study suggests that GIP may contribute to the fasting hyperinsulinemia characteristic of adult obese Zucker rats. GIP infusion to achieve levels equivalent to those seen in the basal state are capable of stimulating insulin release in the absence of hyperglycemia in the obese rat, which suggests an impairment of the regulatory mechanisms controlling the glucose-dependent insulinotropic action of GIP in these animals.
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PMID:Gastric inhibitory polypeptide (GIP) and insulin release in the obese Zucker rat. 637 59

Gastric inhibitory polypeptide (GIP) concentrations may be influenced by obesity, diabetes, and glucagon deficiency and be under feedback inhibition by insulin. To assess these factors, insulin-dependent diabetic, totally pancreatectomized diabetic, and lean and obese noninsulin-dependent diabetic patients were studied twice, once during partial insulin withdrawal and again when euglycemia was achieved before and after mixed meal ingestion, using an artificial endocrine pancreas. The results were compared to those from weight-matched lean and obese nondiabetic subjects. No significant differences in postprandial GIP responses were found between lean and obese nondiabetic subjects. Despite basal and postprandial hyperglycemia, the GIP responses to the mixed meal were not significantly different between insulin-deficient (insulin-dependent and totally pancreatectomized) patients and lean nondiabetic subjects. In addition, there were no significant differences in postprandial GIP responses between insulin-dependent and totally pancreatectomized patients. In contrast, lean and obese noninsulin-dependent diabetic patients had reduced GIP responses compared to weight-matched nondiabetic subjects (mean +/- SE, 37.9 +/- 5.4 vs. 67.1 +/- 10.8 ng ml-1 240 min-1, respectively; P less than 0.05). This difference was entirely due to the reduced GIP responses in obese noninsulin-dependent diabetic patients compared to those in obese nondiabetic subjects (32.1 +/- 7.9 vs. 76.9 +/- 18.2 ng ml-1 240 min-1, respectively; P less than 0.05); the postprandial GIP responses were not significantly different between lean noninsulin-dependent diabetic patients and lean nondiabetic subjects. Insulin infusion by an artificial endocrine pancreas resulted in postprandial insulin and glucose profiles that approximated those of nondiabetics, but did not significantly alter GIP responses to the mixed meal (48.2 +/- 5.5 ng ml-1 240 min-1) in the 18 diabetic patients compared to results obtained with sc insulin treatment (42.2 +/- 5.2 ng ml-1 240 min-1). In conclusion, postprandial GIP responses are normal in obese nondiabetic subjects and insulin-deficient diabetic patients and are blunted in obese, but not in lean, noninsulin-dependent diabetic patients. In addition, GIP does not appear to be under feedback inhibition by insulin or influenced by glucagon deficiency in diabetes.
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PMID:Gastric inhibitory polypeptide in obesity and diabetes mellitus. 637 12

In previous studies on the enteroinsular axis in Zucker rats, it was found that glucose-dependent insulinotropic polypeptide (GIP) levels were normal in obese animals, but the glucose threshold for the insulinotropic action of GIP in the perfused rat pancreas was reduced. Glucagon-like peptide I (GLP-I)(7-36) is also an important incretin, and in the current study, glucose, insulin, and immunoreactive (IR)-COOH-terminal GLP-I responses to oral glucose were compared in lean (Fa/?) and obese (fa/fa) rats. In addition, the concentration thresholds for stimulation and glucose dependence of perfused pancreases to GLP-I(7-36) were examined. Glucose responses to oral glucose were similar in fa/fa and Fa/? rats. Obese animals were hyperinsulinemic when fasting and after oral glucose. Significant increases in IR-GLP-I levels in response to glucose were only observed in fa/fa rats. Perfused pancreases from fa/fa rats hypersecreted insulin at all glucose concentrations. In the presence of 4.4 mmol/l glucose, GLP-I(7-36) increased insulin secretion in fa/fa pancreases approximately 25-fold, whereas there was only a 5-fold increase in Fa/? pancreases. Pancreases from fa/fa rats, perfused with a glucose gradient (2.8-11 mmol/l) in the presence of GLP-I(7-36), responded with an immediate increase in insulin secretion, i.e., at a glucose concentration of 2.8 mmol/l, whereas Fa/? pancreases required a minimum of 4.22 mmol/l glucose for stimulation. With high glucose (16.7 mmol/l), both fa/fa and Fa/? rat pancreases exhibited similar responsiveness to GLP-I(7-36), having thresholds of < 50 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered glucose dependence of glucagon-like peptide I(7-36)-induced insulin secretion from the Zucker (fa/fa) rat pancreas. 772 5

Gastric inhibitory polypeptide (GIP) is one of the strongest insulinotropic gut factors. Its secretion is induced by oral (but not intravenous) glucose and it has been implicated in the pathogenesis of hyperinsulinemic states (NIDDM, obesity). To determine its relevance to hypertension, 54 subjects were studied: 26 normotensives (12 with and 14 without family history of essential hypertension), and 28 essential hypertensive subjects. Plasma glucose, serum insulin (IRI), and GIP were evaluated after a mixed meal containing a total of 82 g of carbohydrates, and 2 g sodium chloride. Venous blood was collected at baseline and every 15 min during a 3-h period. Baseline levels of glucose, IRI, and GIP were comparable in the three groups. At 30 min, however, IRI and GIP were higher in normotensives with a family history of hypertension and in established hypertensive versus control subjects. Both in normotensive and in hypertensive groups, glucose, IRI, and GIP responses to the meal were significantly correlated. Our data suggest the contribution of altered GIP secretion in the pathogenesis of hyperinsulinemia in essential hypertension.
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PMID:Hyperinsulinemia and hypertension. Do intestinal hormones play a role? 775 55

Two studies were performed to assess the entero-insular axis in simple obesity and the possible effect of variations in the level of circulating non-esterified fatty acids (NEFA) on one of the components of the entero-insular axis, glucagon-like peptide-1 [(7-36) amide]. In the first study, we compared the entero-pancreatic hormone response to oral carbohydrate in obese and lean women. Obese subjects demonstrated hyperinsulinaemia and impaired glucose tolerance but this was not associated with an increased secretion of either glucose-dependent insulinotropic polypeptide or glucagon-like peptide-1 (GLP-1). These findings therefore provide no support for the hypothesis that overactivity of the entero-insular axis contributes to the hyperinsulinaemia seen in obesity. Indeed, the plasma GLP-1 response to carbohydrate was markedly attenuated in obese subjects, confirming previous observations. In the second study, in which carbohydrate-stimulated GLP-1 responses were again evaluated in obese and lean women, circulating NEFA levels were modulated using either heparin (to increase serum NEFA) or acipimox (to reduce serum NEFA). Treatment with acipimox resulted in complete suppression of NEFA levels and in a markedly higher GLP-1 response than the response to carbohydrate alone or to carbohydrate plus heparin. We suggest that higher fasting and postprandial NEFA levels in obesity may tonically inhibit nutrient-mediated GLP-1 secretion, and that this results in attenuation of the GLP-1 response to carbohydrate. However, although serum NEFA levels post-acipimox were similarly suppressed in both lean and obese subjects, the GLP-1 response was again significantly lower in obese subjects, suggesting the possibility of an intrinsic defect of GLP-1 secretion in obesity. The reduction of GLP-1 levels in obesity may be important both in relation to its insulinotropic effect and to its postulated role as a satiety factor.
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PMID:Inhibition of carbohydrate-mediated glucagon-like peptide-1 (7-36)amide secretion by circulating non-esterified fatty acids. 1008 39

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), is synthesized and released from the duodenum and proximal jejunum postprandially. Its release depends upon several factors including meal content and pre-existing health status (ie. obesity, diabetes, age, etc.). It was initially discovered and named for its gastric acid inhibitory properties. However, its more physiologically relevant role appears to be as an insulinotropic agent with a stimulatory effect on insulin release and synthesis. Accordingly, it was later renamed glucose-dependent insulinotropic polypeptide because its action on insulin release depends upon an increase in circulating levels of glucose. GIP is considered to be one of the principle incretin factors of the enteroinsular axis. The GIP receptor is a G-protein-coupled receptor belonging to the family of secretin/VIP receptors. GIP receptor mRNA is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex, and brain, suggesting it may have other functions in addition to the ones mentioned above. An overactive enteroinsular axis has been suggested to play a role in the pathogenesis of diabetes and obesity. In addition to stimulating insulin release, GIP has been shown to amplify the effect of insulin on target tissues. In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-stimulated incorporation of fatty acids into triglycerides, (3) increase insulin receptor affinity, and (4) increase sensitivity of insulin-stimulated glucose transport. In addition, although controversial, lipolytic properties of GIP have been proposed. The mechanism of action of GIP-induced effects on adipocytes is unknown, and it is unclear whether these effects of GIP on adipocytes are direct or indirect. However, there is now evidence that GIP receptors are expressed on adipocytes and that these receptors respond to GIP stimulation. Given the location of its release and the timing of its release, GIP is an ideal anabolic agent and expanding our understanding of its physiology will be needed to determine its exact role in the etiology of diabetes mellitus and obesity.
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PMID:GIP biology and fat metabolism. 1066 5

Gastric inhibitory polypeptide (GIP, also called glucose-dependent insulinotropic polypeptide) and glucagon-like peptide-1 (GLP-1) are peptide hormones from the gut that enhance nutrient-stimulated insulin secretion (the 'incretin' effect). Judging from experiments in mice with targeted deletions of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. In patients with type 2 diabetes mellitus it turns out that the incretin effect is severely impaired or abolished. The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired (whereas both the secretion of GIP and the effect of GLP-1 are near normal). The impaired GLP-1 secretion is probably a consequence of diabetic metabolic disturbances. The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic effect of GIP may be found in first degree relatives of the patients, suggesting a genetic background for the defect. The molecular nature of the defect is not known and given the close similarity of the two receptors and their signalling, the dissociation of their effects is remarkable. Whereas GLP-1 and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP receptor do not become obese when exposed to a high-fat diet. Therefore, antagonistic analogues of GIP may be speculated to have a role in the pharmaceutical management of obesity.
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PMID:Gastric inhibitory polypeptide analogues: do they have a therapeutic role in diabetes mellitus similar to that of glucagon-like Peptide-1? 1210 45


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