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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response to plasma immunoreactive gastric inhibitory polypeptide (GIP) to oral glucose loading was determined in 10 normal subjects, 10 patients with mild diabetes mellitus, and 10 patients with moderate to severe diabetes mellitus. In normal subjects the mean fasting GIP was 167 +/- 17 pg/ml which rose significantly after glucose loading, reaching the peak value of 513 +/- 44 pg/ml at 30 min. In mild diabetic patients, fasting plasma GIP was not significantly different from that in normal subjects. However, the mean peak GIP level following glucose loading was 683 +/- 71 pg/ml, significantly higher than that in normal subjects (p less than 0.05). In moderate and severe diabetics, oral glucose loading caused an abrupt rise in plasma GIP from the basal level of 304 +/- 31 pg/ml to the peak of 870 +/- 63 pg/ml occurring at 30 min, both of which were significantly higher than the corresponding values in normal subjects (p less than 0.01). These results suggest that GIP response to oral glucose loading is enhanced in diabetic patients in proportion to the degree of their glucose intolerance.
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PMID:Hypersecretion of gastric inhibitory polypeptide induced by glucose ingestion in diabetes mellitus. 725 66

Glucagon-like peptide 1 (7-37)/(7-36) amide (GLP-1) is derived from the intestinal proglucagon processing. It is considered an important insulin-releasing gut hormone. This study uses exendin (9-39) amide as a GLP-1 receptor antagonist to evaluate the contribution of GLP-1 to the incretin effect. Anesthetized rats were challenged by an intraduodenal glucose infusion to evaluate maximally occurring GLP-1 and gastric inhibitory polypeptide (GIP) plasma levels. Maximal immunoreactive (IR) GLP-1 plasma levels amounted to 10 pmol/l (IR-GIP 11 pmol/l). Exendin (9-39) amide abolished the insulin-stimulatory effect of 60 pmol of GLP-1 or of the GLP-1 agonist exendin-4 (0.5 nmol) injected as bolus, respectively. An intravenous bolus injection of 5.94 nmol of exendin (9-39) amide 3 min before enteral glucose infusion grossly reduced the total insulin secretory response (by 60%) and significantly increased circulating blood glucose levels (P < 0.05). In contrast, the GLP-1 antagonist left the insulin response after an intravenous glucose or glucose plus GIP (60 pmol) load unaltered. Our data support the concept that GLP-1 is an important incretin factor. Exendin (9-39) amide is a useful GLP-1 antagonist for in vivo studies.
Diabetes 1995 Jan
PMID:Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9-39) amide. 781 8

In a previous study we demonstrated that patients with recently diagnosed non-insulin-dependent diabetes mellitus (NIDDM) had significantly increased gastric emptying rates of glucose solutions compared with those of nondiabetic sex- and age-matched controls. This finding of rapid gastric emptying contrasts with the delayed gastric emptying often exhibited as a late manifestation of diabetes mellitus that is attributed to autonomic neuropathy. The purpose of this study was to determine, in seven of the patients previously studied, whether (1) an intravenous infusion of cholecystokinin-8 (CCK-8) would delay the gastric emptying of a liquid glucose meal and, if so, (2) whether the delay in gastric emptying would result in reduced postprandial blood glucose concentrations due to prolongation of the absorption of the glucose in the liquid meal. Each patient underwent two separate gastric emptying studies, one during a saline infusion and one during a CCK-8 infusion. Blood samples were obtained at 15-min intervals for measurement of glucose, insulin, CCK-8, and gastric inhibitory polypeptide (GIP) concentrations. The average gastric half-emptying time was 41 min with the saline infusion and 94 min with the CCK-8 infusion (P = 0.0042). The average glucose concentration over the 2-hr period following glucose ingestion was 17.1 mmol/liter with the saline infusion and 14.0 mmol/liter with the CCK-8 infusion (P = 0.0073). The average glucose excursion value over the 2-hr period was reduced from 5.6 mmol/liter to 3.7 mmol/liter with the CCK-8 infusion (P = 0.0550).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced postprandial blood glucose levels in recently diagnosed non-insulin-dependent diabetics secondary to pharmacologically induced delayed gastric emptying. 842 Jul 60

Postprandial insulin secretion is modulated by both neural and humoral gastrointestinal insulinotropic factors in addition to the absorbed nutrient. To investigate the involvement of the potent insulinotropic hormones gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1) in the postprandial hyperinsulinaemia of obesity, we examined the changes in plasma levels of GIP and tGLP-1 by an oral glucose tolerance test (OGTT) in nine normal subjects (controls), nine obese subjects without glucose intolerance (Group A), and six obese mild diabetic patients (Group B). Following the OGTT, plasma GIP levels in Group B were increased more markedly than those in the other two groups. Plasma levels of tGLP-1 were estimated by the difference between the values measured with the N-terminal directed antiserum (GLP-1NT) and those with the C-terminal directed antiserum (GLP-1 CT). Plasma levels of GLP-1 NT were increased in Group B, but decreased in the other two groups. Plasma GLP-1 CT levels were increased in all groups with the highest response in Group B. These results suggest that the combined augmentation of plasma GIP and tGLP-1 responses were involved in the delayed and considerable increases in plasma insulin after glucose ingestion in obese diabetic patients. Since tGLP-1 is suppressed in the hyperglycaemic hyperinsulinaemic state in normal subjects, the augmented tGLP-1 response appears to be characteristic of obese Type 2 diabetes.
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PMID:Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients. 843 87

The incremental glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses (areas under curves; AUCs) were determined during a standard 180-min 75-g oral glucose tolerance test in a group of 12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) and 13 matched controls without family history of diabetes using highly sensitive and specific radioimmunoassay hormone assays. Data were analysed using multifactor analysis of variance (ANOVA) to identify and correct for possible covariates and to correct for multiple comparisons. Fasting plasma GLP-1 and GIP concentrations were similar in all groups. The twins with frank NIDDM had a decreased incremental GLP-1 response during oral glucose ingestion compared with controls without family history of diabetes (AUC +/- SEM: 0.55 +/- 0.14 vs 1.17 +/- 0.25 (mmol/l) x min, p < 0.05). The incremental GLP-1 secretion in the non-diabetic twins was not significantly different from neither their NIDDM co-twins nor the controls without family history of diabetes. The incremental GIP responses were similar in all study groups. Gender was identified as the major independent covariate for incremental glucose, insulin, GIP and GLP-1 responses, with higher values of all parameters in females. Waist-to-hip ratio and body mass index (BMI) were identified as independent but oppositely directed covariates for the incremental GLP-1 responses (waist-to-hip ratio: r = 0.43, p < 0.02; BMI: r = -0.34, p = 0.06). Incremental GLP-1 responses correlated with incremental insulin responses in the combined study population (N = 37; R = 0.42, p = 0.01). In conclusion, a decreased intestinal GLP-1 secretion may contribute to the abnormal insulin secretion during oral glucose ingestion in NIDDM twins. However, decreased secretion of gut incretin hormones (GLP-1 or GIP) does not explain all of the defects of pancreatic insulin secretion in NIDDM patients/twins or in non-diabetic individuals (identical twins) with a genetic predisposition to NIDDM.
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PMID:Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)--evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins. 892 24

Fourteen patients with non-insulin-dependent diabetes (NIDDM) attended the study centre on 4 mornings separated by at least 3 days, to receive in random order 75 g carbohydrate breakfast meals of control or guar breads with jam and butter. Guar gum flours of low, medium, and high molecular weight (MW) were incorporated into wheat bread rolls to provide 7.6 g guar per meal. Venous blood samples were taken via an indwelling cannula in a forearm vein at fasting and at eight postprandial times and then analysed for blood glucose, plasma insulin, C-peptide, and gastric inhibitory polypeptide (GIP). Guar gum bread significantly reduced the postprandial rise in blood glucose, plasma insulin, and, except for bread containing low MW guar gum, plasma GIP levels compared to the control. Thus, the partial depolymerization of guar gum does not diminish its physiological activity. No reductions in postprandial plasma C-peptide levels were seen after any of the guar bread meals. This suggests that guar gum attenuates the insulin concentration in peripheral venous blood in patients with NIDDM by increasing the hepatic extraction of insulin.
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PMID:Effect of partially depolymerized guar gum on acute metabolic variables in patients with non-insulin-dependent diabetes. 916 12

Oral administration of a single dose of triphenyltin compounds induces diabetes with decreased insulin secretion in rabbits and hamsters after 2-3 days without any morphological changes in pancreatic islets. In the present study, to test the possibility that the impaired insulin secretion induced by triphenyltin compounds could result from an impaired Ca2+ response in pancreatic beta-cells, we investigated the effect of triphenyltin-chloride (TPTCl) administration on the changes in the cytoplasmic Ca2+ concentration ([Ca2+]i) induced by secretagogues, such as glucose, high K+, gastric inhibitory polypeptide (GIP), and acetylcholine (ACh) in hamster pancreatic beta-cells. TPTCl administration caused partial suppression in 10 mM K+-induced rise in [Ca2+]i without suppressing the increase in [Ca2+]i evoked by 20-50 mM K+. Administration of TPTCl strongly inhibited the rises in [Ca2+]i induced by 27.8 mM glucose, 100 microM ACh in the presence of 5.5 mM glucose, and by 100 nM GIP in the presence of 5.5 mM glucose. In the ACh-induced response, TPTCl administration strongly suppressed the late sustained phase, while weakly suppressing the initial rise in [Ca2+]i. TPTCl administration significantly suppressed the rise of cAMP content in islet cells induced by 100 nM GIP with 1 mM 3-isobutyl-1-methylxanthine in the presence of 5.5 mM glucose (P < 0.01, N = 5-11). TPTCl administration also impaired the insulin secretion in islet cells induced by 27.8 mM glucose, 100 nM GIP in the presence of 5.5 mM glucose, and 100 microM ACh in the presence of 5.5 mM glucose (P < 0.05, N = 9-16). We conclude that the pathology of triphenyltin-induced diabetes in hamsters involves a defect in cellular Ca2+ response due to a reduced Ca2+-influx through voltage-gated Ca2+ channels.
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PMID:Impaired cytosolic Ca2+ response to glucose and gastric inhibitory polypeptide in pancreatic beta-cells from triphenyltin-induced diabetic hamster. 920 16

Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone in normal humans explaining in part the augmented insulin response after oral versus intravenous glucose administration. In addition, GLP-1 also lowers glucagon concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis, reduces food intake upon intracerebroventricular administration in animals, and may, in addition, enhance insulin sensitivity. Therefore, GLP-1, in many aspects, opposes the Type 2-diabetic phenotype characterized by disturbed glucose-induced insulin secretory capacity, hyperglucagonaemia, moderate insulin deficiency, accelerated gastric emptying, overeating (obesity) and insulin resistance. The other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all its activity in Type 2-diabetic patients. In contrast, GLP-1 glucose-dependently stimulates insulin secretion in diet- and sulfonylurea-treated Type 2-diabetic patients and also in patients under insulin therapy long after sulfonylurea secondary failure. Exogenous administration of GLP-1 ([7-37] or [7-36 amide]) in doses elevating plasma concentrations to approximately 3-4 fold physiological postprandial levels fully normalizes fasting hyperglycaemia in Type 2-diabetic patients. The half life of GLP-1 is too short to maintain therapeutic plasma levels for sufficient periods by subcutaneous injections. Current research activities aim at finding GLP-1 analogues with more suitable pharmacokinetic properties than the original peptide. Another approach could be the augmentation of endogenous release of GLP-1, which is abundant in L cells of the lower small intestine and the colon. Interference with sucrose digestion using alpha-glucosidase inhibition moves nutrients into distal parts of the gastrointestinal tract and, thereby, prolongs and augments GLP-1 release. Enprostil, a prostaglandin E2 analogue, fully suppresses GIP responses, while only marginally affecting insulin secretion and glucose tolerance after oral glucose, suggesting compensatory hypersecretion of additional insulinotropic peptides, possibly including GLP-1. Given the large amount of GLP-1 present in L cells, it appears worthwhile to look for more agents that could 'mobilize' this endogenous pool of the 'antidiabetogenic' gut hormone GLP-1.
Exp Clin Endocrinol Diabetes 1997
PMID:Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for type 2-diabetes. 928 4

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.
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PMID:Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. 1061

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


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