UMLS:C0011860 - FACTA Search

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Newly diagnosed, previously untreated patients with type 2 diabetes mellitus (n = 6) were studied on two separate days after overnight fasts. On each day they were given a 500-kcal mixed meal plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (GIP) (0.75 pmol/kg/min) or control solution (CS) from 0 to 30 min in random order. Frequent measurements of plasma glucose, C-peptide, insulin and GIP concentrations were made. Fasting GIP levels were similar on both days. During the meal plus GIP infusion plasma GIP levels increased from a basal value of 7.6 +/- 1.5 pmol/1 to a peak of 88.6 +/- 5.4 pmol/1 at 30 min. Following the meal infusion of CS GIP increased from a fasting level of 10.3 +/- 1.2 pmol/1 to a significantly lower peak of 58.0 +/- 8.3 pmol/1 at 60 min. During the meal plus GIP infusion GIP levels were higher at 10-45 min and at 90 min (P less than 0.05-0.001). Fasting and postprandial glucose, C-peptide and insulin levels were, however, similar on both study day. A supplementary infusion of porcine GIP with a mixed meal did not significantly alter the beta cell response or glucose tolerance in this group of patients with type 2 diabetes mellitus.
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PMID:A supplementary infusion of glucose-dependent insulinotropic polypeptide (GIP) with a meal does not significantly improve the beta cell response or glucose tolerance in type 2 diabetes mellitus. 269 29

Gastric inhibitory polypeptide (GIP) has insulinotropic actions in the presence of hyperglycemia. However, its extrapancreatic effects on glucose homeostasis are controversial. We have studied the relationships between GIP and immunoreactive insulin (IRI) and glucose turnover rates (D3H-3 glucose technique) in five poorly controlled type II diabetic patients and five normal subjects before and after a breakfast containing 500 kcal including 42 g sucrose. Mean fasting serum glucose levels and glucose responses were significantly (P less than 0.001) higher in the diabetic patients than in normal subjects. Mean basal serum IRI levels were similar in both groups [12.8 +/- 2.9 (SEM) vs. 11.8 +/- 2 microU/ml, P = NS]. After meal ingestion, mean IRI levels rose significantly to a peak at 20 min in the normal subjects but the responses were blunted in the diabetic patients (74 +/- 10 vs. 24 +/- 6 microU/ml, P less than 0.001). At all other times studied (60-180 min), mean serum IRI levels were similar in the diabetic patients and the normal subjects except at 180 min. Mean basal serum GIP levels were similar in the diabetic patients and the normal subjects (538 +/- 100 vs. 400 +/- 50 pg/ml, P = NS). After meal ingestion, mean GIP levels rose between 0-60 min but were significantly higher in the diabetic patients only at 20 min (1200 +/- 190 vs. 566 +/- 76 pg/ml, P less than 0.01). Mean basal hepatic glucose output was higher (P less than 0.01) in the diabetic patients. However, the mean basal MCR values were similar. After meal ingestion, total splanchnic glucose output and rates of glucose utilization (RU) were significantly higher in the diabetic patients compared with the normal subjects (P less than 0.001, and P less than 0.001, respectively). Postmeal MCR values were not statistically different in both groups. There were significant positive correlations between postmeal splanchnic glucose output and both IRI (r = 0.805, P less than 0.005) and GIP (r = 0.749, P less than 0.02) in the diabetic patients but not in the normal subjects (r = 0.10, P = NS for both). Whereas no relationships existed between RU and IRI in either group, RU correlated strongly with GIP (r = 0.810, P less than 0.005) only in the diabetic patients. We hypothesize that GIP may play a compensatory role to improve both impaired beta-cell insulin release and peripheral glucose utilization which are the recognized pathogenetic mechanisms underlying type II diabetes mellitus.
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PMID:Gastric inhibitory polypeptide responses and glucose turnover rates after natural meals in type II diabetic patients. 351 Feb 24

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 466 amino acids which showed high homology (41%) to the human glucagon-like peptide 1 (GLP-1) receptor. Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. When transfected stably into fibroblast CHL-cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under stimulation with human GIP-1-42 (EC50 = 1.29 x 10(-13) M). The receptor accepted only human GIP 1-42 (Kd = 1.93 +/- 0.2 x 10(-8) M) and porcine truncated GIP 1-30 (Kd = 1.13 +/- 0.1 x 10(-8) M) as high affinity ligands. At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. In transfected CHL cells, GIP-1-42 did not increase intracellular calcium. Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus.
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PMID:Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. 758 26

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

Despite similar glycemic profiles, higher insulin levels are achieved following oral versus intravenous administration of glucose. This discrepancy is due to the incretin effect and is believed to be mediated via stimulation of beta-cells by hormone(s) released from the gut. The leading gut hormone candidates are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1). To determine the relative insulinotropic activity of these peptides, we infused GLP-1(7-37) and GIP into normal subjects and patients with non-insulin dependent diabetes mellitus (NIDDM). In normal subjects during euglycemia, GLP-1(7-37) stimulated insulin release, whereas GIP did not. Using the Andres clamp technique, we established stable hyperglycemia for 2 h (5.4 mmol/l above the basal level). During the second hour, either GIP, GLP-1(7-37), or both were infused in normal healthy volunteers and in patients with NIDDM. In normal subjects, at a glucose level of 10.4 mmol/l, the 90-120 min insulin response was 279 pmol/l. GIP at a dose of 1, 2 or 4 pmol/kg/min augmented the 90-120 min insulin response by 69, 841 and 920 pmol/l, while GLP-1(7-37), at a dose of 1.5 pmol/kg/min augmented the insulin response by 2106 pmol/l. When both hormones were administered simultaneously, the augmentation was additive--2813 pmol/l. In the diabetic subjects, GIP had no effect, while GLP-1(7-37) augmented the insulin response by 929 pmol/l. We conclude that in normal healthy subjects, GLP-1(7-37), on a molar basis, is several times more potent than GIP at equivalent glycemic conditions. The additive insulinotropic effect suggests that more than one incretin may be responsible for the greater insulin levels observed following oral administration of glucose compared to the intravenous route. In NIDDM, GIP had no insulinotropic effect, while GLP-1(7-37) had a marked effect. This suggests that GLP-1(7-37) may have therapeutic potential as a hypoglycemic agent in NIDDM patients.
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PMID:The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. 803 84

Gastric inhibitory polypeptide (tGIP) and truncated glucagon like peptide-1 (GLP-1) are potent gastrointestinal insulinotropic factors (incretin), are most released after a meal or ingestion of glucose in man and animals. To investigate whether sulfonylurea (SU) affects the secretion of incretin, the modulation of plasma GIP and tGLP-1 levels following glucose ingestion in non-insulin-dependent diabetic type 2 patients with or without SU therapy was studied. A 75-G oral glucose tolerance test (OGTT) was carried out on 9 healthy subjects (controls) and 18 patients with non-obese type 2, 9 of whom were treated by diet alone (NIDDM-diet) and the other 9 with SU (glibenclamide 2.5 mg or gliclazide 40 mg) once a day (NIDDM-SU). Plasma GIP was measured by radioimmunoassay (RIA) with R65 antibody, and GLP-1 was measured by RIA with N-terminal-directed antiserum R1043 (GLP-1NT) and C-terminal-directed antiserum R2337 (GLP-1CT). Following OGTT, plasma glucose, GIP, GLP-1NT, and GLP-1CT in type 2 patients increased more markedly than in controls, despite the lower response of insulin. However, there were no significant differences in plasma levels of these peptides between the NIDDM-diet and NIDDM-SU groups. Therefore, it is unlikely that SU is involved in the high response of GIP and GLP-1s to OGTT in type 2 patients.
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PMID:Response of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide to glucose ingestion in non-insulin dependent diabetes mellitus. Effect of sulfonylurea therapy. 859 Jul 85

Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). We have identified two missense mutations, Gly198-->Cys (Gly198Cys) in exon 7 and Glu354-->Gln (Glu354Gln) in exon 12. Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. Association studies show no relationship between NIDDM and either of the two mutations.
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PMID:Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. 892 54

We have studied the impact of liquid diets formulated for complete or supplemental enteral nutrition of type II, non insulin-dependent (NIDDM) diabetics on carbohydrate homeostasis. To achieve this, liquid formula tolerance tests were performed in NIDDM patients under an oral treatment regimen with a combination of diet plus glibenclamide (7 men, 3 women, age: 56 +/- 11 years; mean body mass index of 26.2 +/- 3.6 kg/m2). After an overnight fast, each patient received the usual morning medication and, thereafter, ingested formula diet in randomized order with 10 day intervals between tests. 500 ml were administered of either a standard liquid diet (Biosorb Sonde), a fibre containing diet (Biosorb Plus Sonde), or a carbohydrate modified, fructose containing "diabetes" diet (Fresubin Diabetes) (carbohydrate contents of approximately equal to 60 g, respectively). Blood samples were collected over 180 min. Considering minor variations in the nutritional values of the diets, IR-insulin, IR-C-peptide, IR-glucose-dependent insulinotropic polypeptide (GIP), and IR-glucagon-like peptide. 1 (GLP-1) in plasma did not significantly differ between the study groups. After ingestion of Biosorb Sonde area under the curve glucose was greater than that seen after uptake of fibre containing or carbohydrate modified, i.e. fructose containing "liquid diabetes diets". All diets challenged the entero-insular axis in non-insulin dependent diabetics to a comparable extent. This data does not support the contention to employ special "diabetes" formulas for enteral nutrition of patients with NIDDM.
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PMID:No apparent benefit of liquid formula diet in NIDDM. 922 8

The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1 act on the pancreas to potentiate glucose-induced insulin secretion (enteroinsular axis). These hormones (incretins) are rapidly hydrolyzed by the circulating enzyme dipeptidyl peptidase IV (DP IV) into biologically inactive NH2-terminally truncated fragments. This study describes the effect of inhibiting endogenous DP IV with a specific DP IV inhibitor, isoleucine thiazolidide (Ile-thiazolidide), on glucose tolerance and insulin secretion in the obese Zucker rat. In initial studies, the specificity of Ile-thiazolidide as an inhibitor of incretin degradation was determined using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. These results showed that inhibiting DP IV activity with Ile-thiazolidide blocked the formation of NH2-terminally truncated GIP and GLP-1. Oral administration of Ile-thiazolidide resulted in rapid inhibition of circulating DP IV levels by 65% in obese and lean Zucker rats. Suppression of DP IV levels enhanced insulin secretion in both phenotypes with the most dramatic effect occurring in obese animals (150% increase in integrated insulin response vs. 27% increase in lean animals). Ile-thiazolidide treatment improved glucose tolerance in both phenotypes and restored glucose tolerance to near-normal levels in obese animals. This was attributed to the glucose-lowering actions of increasing the circulating half-lives of the endogenously released incretins GIP and, particularly, GLP-1. This study suggests that drug manipulation of plasma incretin activity by inhibiting the enzyme DP IV is a valid therapeutic approach for lowering glucose levels in NIDDM and other disorders involving glucose intolerance.
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PMID:Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide. 970 25

The incretins glucose-dependent insulinotropic polypeptide (GIP1-42) and truncated forms of glucagon-like peptide-1 (GLP-1) are hormones released from the gut in response to ingested nutrients, which act on the pancreas to potentiate glucose-induced insulin secretion. These hormones are rapidly inactivated by the circulating enzyme dipeptidyl peptidase IV ([DPIV] CD26). This study describes the effect on glucose tolerance and insulin secretion of inhibiting endogenous DPIV in the rat using Ile-thiazolidide, a specific DPIV inhibitor. High-performance liquid chromatography (HPLC) analysis of plasma following in vivo administration of 125I-labeled peptides showed that inhibition of DPIV by about 70% prevented the degradation of 90.0% of injected 125I-GLP-17-36 after 5 minutes, while only 13.4% remained unhydrolyzed in rats not treated with the DPIV-inhibiting agent after only 2 minutes. Ile-thiazolidide treatment also increased the circulating half-life of intact GLP-17-36 released in response to intraduodenal (ID) glucose (as measured by N-terminal specific radioimmunoassay [RIA]). In addition, inhibition of DPIV in vivo resulted in an earlier increase and peak of plasma insulin and a more rapid clearance of blood glucose in response to ID glucose challenge. When considered with the HPLC data, these results suggest that the altered insulin profile is an incretin-mediated response. DPIV inhibition resulting in improved glucose tolerance may have therapeutic potential for the management of type 2 diabetes mellitus.
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PMID:Improved glucose tolerance in rats treated with the dipeptidyl peptidase IV (CD26) inhibitor Ile-thiazolidide. 1009 18

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