Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Diabetes 1984 Jun
PMID:Gastric inhibitory polypeptide (GIP) and insulin release in the obese Zucker rat. 637 59

The effect of insulin on fat-induced gastric inhibitory polypeptide (GIP) release has been studied in seven healthy volunteers during euglycemic blood glucose clamping. In the first protocol, insulin (0.1 U/kg/h) was infused 2 h before ingestion of 100 g fat and continued for 2 h thereafter. In protocol II, saline was infused 2 h before the fat load and the insulin infusion started at the time of fat ingestion. During both insulin infusion studies, glucose levels were clamped at the fasting level by means of the Biostator and plasma levels of insulin, C-peptide, and GIP were estimated by radioimmunoassay. The response of GIP to oral fat was inhibited by 63% if insulin infusion was started at the time of fat ingestion, whereas no inhibition was seen if a 2-h hyperinsulinemic period preceded the fat load. The plasma insulin levels were comparable at the end of each experiment, ranging from 110 to 130 microU/ml. Plasma C-peptide levels decreased during the insulin infusion and increased after fat ingestion. These findings were not the result of inhibition of gastric emptying by insulin because they could be confirmed in four volunteers with intraduodenal infusion of fat. The present data show that insulin does inhibit fat-induced GIP secretion in normal man, but preceding hyperinsulinemic glucose clamping masks this insulin effect, probably by decreasing the sensitivity of the GIP cells to insulin.
Diabetes 1984 Jun
PMID:Preceding hyperinsulinemia prevents demonstration of insulin effect on fat-induced gastric inhibitory polypeptide (GIP). 637 62

The effect of aging, obesity, and non-insulin-dependent diabetes mellitus on glucose-stimulated gastric inhibitory polypeptide (GIP) levels was studied in 55 male subjects, ranging in age from 19 to 84 yr, and in obesity, expressed as body mass index, from 21 to 34. Studies were performed using the hyperglycemic glucose clamp technique, in which the blood glucose was maintained at 125 mg/dl above basal for 2 h. Glucose (40 g/m2 body surface) was ingested at 60 min. Plasma immunoreactive GIP (IR-GIP) did not change during intravenous (i.v.) glucose alone, but began to rise within 10 min after glucose ingestion and reached a peak at 30-40 min. Basal and stimulated IR-GIP levels were markedly elevated in diabetic subjects and modestly elevated in obese subjects, compared with appropriately matched controls. In contrast, age had little effect on plasma IR-GIP levels either in the basal state or after glucose ingestion. When IR-GIP responses to oral glucose were expressed as a relative change from basal levels, IR-GIP rose 86% in diabetic subjects and 243% in obese subjects, compared with 185% and 165% in their respective controls. IR-GIP rose 179% in young subjects and 144% in middle-aged subjects, while, in old subjects, the increase was 265%. Plasma IRI levels were reduced in the diabetic subjects, slightly elevated in obese subjects, and were similar in older and younger subjects. Beta cell sensitivity to endogenous GIP decreases with age, and is unchanged in both obesity and nonmedicated diabetes.
Diabetes 1984 Oct
PMID:The enteric enhancement of glucose-stimulated insulin release. The role of GIP in aging, obesity, and non-insulin-dependent diabetes mellitus. 638 4

Previous reports have documented the fact that plasma glucose and insulin responses can vary in response to the ingestion of different carbohydrate-rich foods. This has led to the creation of a "glycemic index," a classification of dietary carbohydrates on the basis of the relative rise in plasma glucose after the administration of the food in question as compared to a standard glucose challenge. In order to test the clinical utility of these observations, we evaluated plasma glucose, insulin, and gastric inhibitory polypeptide responses to four major sources of carbohydrate (potato, rice, spaghetti, lentil) as part of a conventional mixed meal in patients with noninsulin-dependent diabetes mellitus. Each test meal provided 40% of the subjects' calculated caloric requirement and contained 15% of total calories as protein, 40% as fat, and 45% as carbohydrate. The test carbohydrate represented 66% of total carbohydrate. The results indicated that plasma glucose concentrations after meals containing equal amounts of carbohydrate as rice, spaghetti, or lentil were similar and somewhat lower than meals containing potato. The plasma insulin responses to the four carbohydrate foods paralleled the glucose responses. Changes in gastric inhibitory polypeptide levels did not account for the effect of potato. These results are totally disparate from what would have been predicted by previously published values for the "glycemic index" of the four foods studied, and suggest that a "glycemic index" based on isolated challenges would have minimal clinical utility in efforts aimed at reducing postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus.
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PMID:Effect of source of dietary carbohydrate on plasma glucose, insulin, and gastric inhibitory polypeptide responses to test meals in subjects with noninsulin-dependent diabetes mellitus. 638 5

The glucose load of the oral glucose tolerance test (OGTT) is well standardized. However, recommendations on rate of ingestion and nature of the load are vague. In this study the effect on blood glucose, serum insulin, C-peptide, and plasma gastric inhibitory polypeptide (GIP) of giving 75 g glucose in 300 ml over 1 and 10 min (G1 and G10) was investigated in six subjects. In five an isocaloric amount of partially hydrolyzed starch (Hycal) was also used (H1 and H10). The fast glucose intake, compared with the slow ingestion, resulted in an earlier rise in blood glucose levels, accompanied by a faster serum insulin and C-peptide response. Between 90 and 135 min blood glucose concentrations were significantly higher after the 10-min glucose intake. At 120 min blood glucose levels were 5.5 +/- 0.5 and 4.7 +/- 0.5 mmol/L, respectively, for G10 and G1 (P less than 0.05). In the first half hour after slow and fast Hycal intake no differences were seen in blood glucose, serum insulin, and C-peptide levels. Between 45 and 120 min blood glucose levels were significantly higher after the 10-min Hycal intake. At 120 min blood glucose levels were 5.3 +/- 0.2 and 4.4 +/- 0.1 mmol/L, respectively, for H10 and H1 (P less than 0.01). Except for a faster rise in glucose and insulin levels after glucose loading in 1 min, no further differences were found, when compared with Hycal. No significant differences were seen in the GIP responses. Thus differences in rates of ingestion can cause significant differences in later results. A standard time for glucose ingestion should be specified.
Diabetes Care
PMID:The oral glucose tolerance test (OGTT): effect of rate of ingestion of carbohydrate and different carbohydrate preparations. 640 Jul 3

To evaluate the role of gastric inhibitory polypeptide (GIP) in the augmented insulin response to sucrose, seven normal volunteers ingested four separate meals of 100 g sucrose (S), 50 g glucose (G), 50 g fructose (F), and 50 g glucose + 50 g fructose (G + F). Serum insulin, glucose, and GIP were measured. In each of the 3 h after sugar ingestion the integrated insulin response to (S) was greater than to (G) with the 3-h total being 104% greater. The integrated glucose response to (S) was slightly greater than to (G) in the first and second hours but the differences were not significant. Integrated GIP response to (S) was greater than to (G) in hours 2 and 3. Although significant insulin and glucose responses to (F) occurred in hour 1, G + F led to insulin and glucose responses similar to G. G + F led to greater GIP levels than G in hour 3. These studies show that GIP may play a role in the augmented insulin response to S in hours 2 and 3. This may result from delayed gastric emptying and glucose absorption. The augmentation of insulin to S in the first hour may result from fructose, extra glucose equivalent of the sucrose test solution, or from endocrine mechanisms other than those subserved by GIP.
Diabetes Care
PMID:The role of gastric inhibitory polypeptide in the augmented insulin response to sucrose. 675 77

The effect of glucose and insulin on fat- and glucose-induced gastric inhibitory polypeptide (GIP) release has been studied in insulin-dependent juvenile-type diabetics. Blood glucose and serum immunoreactive GIP (IR-GIP) were measured after an oral load of 100 g glucose or 100 g fat was given and during an infusion of one of the following: saline, glucose, glucose plus insulin, or insulin. The infusion of insulin alone (in the presence of elevated glucose levels) or together with glucose significantly suppressed the IR-GIP rise after fat ingestion, but it did not alter the GIP response to oral glucose. Intravenous infusion of glucose had a slight but significant inhibitory effect on fat-stimulated increase of IR-GIP, which cannot be related to endogenous insulin release in these insulin-deficient diabetics. It is suggested that an insulin-mediated increase of glucose utilization in the GIP cell interferes only with increased GIP secretion stimulated by the utilization of fatty acids but not of glucose. This could explain the existence of a negative feedback control between insulin and GIP secretion for fat but not for glucose-induced GIP release.
Diabetes 1980 Feb
PMID:Inhibition of gastric inhibitory polypeptide (GIP) release by insulin and glucose in juvenile diabetes. 698 99

In most morbidly obese patients with diabetes, fasting plasma glucose levels decreased immediately after jejunoileal bypass operations, with patients often becoming normoglycemic before discharge from the hospital. All 12 patients who had required insulin or orally administered hypoglycemic agents preoperatively were able to discontinue the medication shortly after the operation. Oral glucose tolerance test curves in all morbidly obese patients had a flattened pattern, in the normal range, postoperatively. Serum insulin levels, which had been elevated preoperatively, decreased significantly, both in fasting and postglucose determinations. Results of intravenous glucose tolerance tests showed little change in the early period after operation. Improvement in carbohydrate metabolism may be due to several factors and does not appear to be dependent upon massive weight loss. Major factors may include decreased absorption of carbohydrates and amino acids, decreased oral caloric intake, increased insulin sensitivity and decreased output of gastric inhibitory polypeptide as well as the eventual weight loss.
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PMID:Observations on the improvements in carbohydrate metabolism in diabetic and other morbidly obese patients after jejunoileal bypass. 701 22

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.
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PMID:Gastric inhibitory polypeptide release after oral glucose: relationship to glucose intolerance, diabetes mellitus, and obesity. 704 54

The increased incidence of severe hypoglycemia reported in young children with diabetes is consistent with a defect in glucagon secretion or a generalized abnormality in islet hormone secretion. To assess pancreatic hormone and gastric inhibitory polypeptide secretion in children with early onset diabetes, 12 children with onset of diabetes prior to the age of 28 months were studied and the data compared to the hormone responses observed in 11 children with LOD, diagnosed after the age of 5 years. Plasma glucose, C-peptide, glucagon, pancreatic polypeptide, and gastric inhibitory peptide concentrations were measured during and following an arginine infusion (500 mg/kg over 60 minutes) and a mixed meal. During arginine infusion, plasma glucose and glucagon increased similarly in both groups and returned to basal concentrations following discontinuation of arginine infusion. In contrast, plasma C-peptide, hPP, and GIP concentrations did not change. Following the mixed meal plasma glucose, hPP, and GIP concentrations increased similarly in the two groups of children, but no change was observed in either plasma glucagon or C-peptide concentrations in either group. These data demonstrate that EOD and LOD are associated with insulin insufficiency alone and that abnormalities in secretion of other pancreatic islet hormone or GIP cannot be implicated in the high incidence of severe hypoglycemia observed in children with EOD.
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PMID:Endocrine pancreatic response of children with onset of insulin-requiring diabetes before age 3 and after age 5. 704 15


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