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)

Effect of synthetic gastric inhibitory polypeptide (GIP) on insulin and glucagon secretion was stuied in vivo and in vitro in the rat. Intravenous administration of 1 microng./kg. GIP along with 0.625 gm./kg. glucose caused a more prominent rise of plasma insulin than did 0.625 gm./kg. glucose alone. The suppression of plasma glucagon levels induced by glucose was attenuated partially but not significantly by the concomitant administration of GIP. GIP (1 microng./kg. i.v.) alone raised both plasma insulin and glucago levels. In in-vitro experiments with isolated pancreatic islets, GIP significantly augmented insulin release induced by either 8.3 mM or 16.7 mM glucose, whereas the augmentation of glucagon release was observed at 3.3 mM, 8.3 MM, and 16.7 mM glucose concentrations. Three peptides, consisting of 1-28, 22-43, and 15-43 amino acids of GIP, failed to potentiate insulin and glucagon secretion. These results suggest that synthetic GIP has a stimulating effect on insulin and glucagon secretion.
Diabetes 1977 May
PMID:Synthetic gastric inhibitory polypeptide. Stimulatory effect on insulin and glucagon secretion in the rat. 32 91

Gastric inhibitory polypeptide (GIP) is insulinotropic and is released after ingestion of glucose in normal man. Changes in plasma immunoreactive gastric inhibitory polypeptide (IRGIP) were therefore studied during a 50-gm. oral glucose tolerance test in 10 normal subjects and 20 subjects with maturity-onset diabetes mellitus. The diabetics were nonobese and treated by diet alone; they exhibited exaggerated increments of plasma IRGIP in association with delayed and diminished peak increases in plasma immunoreactive insulin, suggesting relative failure of the beta-cell response to GIP. The diabetic subjects also showed a paradoxic rise in mean plasma immunoreactive glucagon, with a peak coinciding with that of plasma IRGIP. It is suggested that the defective beta-cell response may lead to diminished feedback inhibition of GIP secretion by insulin in diabetes mellitus and that the glucagonotropic action of GIP may be expressed under these conditions.
Diabetes 1977 Jun
PMID:Hypersecretion of gastric inhibitory polypeptide following oral glucose in diabetes mellitus. 32 34

The response of gastric inhibitory polypeptide (GIP) levels to oral glucose in 11 insulin-dependent diabetics was compared to that in 8 age- and sex-matched healthy controls to determine whether they would show the pattern of GIP hypersecretion reported by other workers in maturity-onset, insulin-independent diabetes. One gram of glucose per kg bw resulted in a higher level of glycemia and a significantly diminished GIP response in diabetics when compared to controls (6,018 +/- 1,337 vs. 11,343 +/- 2,353 pg/ml.180 min min, respectively). There was virtually no beta cell response in the diabetics, as measured by changes in the levels of free insulin and connecting peptide. A significant lowering of glucagon levels occurred in the controls, while an inconsistent response was seen in the diabetics. An insulin infusion test was administered to test the hypothesis that insulin suppresses GIP secretion. Although hyperinsulinism, hypoglycemia, and suppression of endogenous insulin secretion were produced in the controls, no suppression of baseline GIP was detected. Similarly, hyperinsulinism and hypoglycemia failed to suppress baseline GIP levels in the diabetics. These results do not support a direct role for insulin in suppressing GIP in normal or diabetic subjects.
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PMID:Gastric inhibitory polypeptide response to hyper- and hypoglycemia in insulin-dependent diabetics. 45 45

Fat feeding stimulated the release of gastric inhibitory polypeptide (GIP) without concomitant insulin secretion. Since antilipolytic effects of GIP have been demonstrated and the uptake of triglyceride fatty acid by adipose tissue postprandially is a process reciprocally regulated with lipolysis, a stimulatory role of GIP on adipose tissue lipoprotein lipase activity may be present. After cultured preadipocytes were incubated for 2 h with GIP, the release of lipoprotein lipase activity into the culture medium and the total cellular activity present in acetone-ether powders of cells were measured. GIP stimulated significant increases in the lipoprotein lipase activity released into the culture medium and in cells. A dose response relationship was strongest for the effect of GIP on the enzyme activity in extracts of acetone-ether powders of the cells. The increased lipoprotein lipase activity produced by GIP could provide a mechanisms for clearance of chylomicron triglyceride after feeding in man.
Diabetes 1979 Dec
PMID:Gastric inhibitory polypeptide enhanced lipoprotein lipase activity in cultured preadipocytes. 51 Aug 13

Responses of plasma immunoreactive gastric inhibitory polypeptide (IRGIP) to oral triglyceride or galactose were compared in normal and mildly diabetic (non-insulin-dependent) subjects. After triglyceride the responses of IRGIP were similar, but after galactose those of the diabetics were slightly exaggerated. Both stimuli evoked increments of plasma immunoreactive glucagon (IRG) in diabetics but not in normal subjects. Plasma immunoreactive insulin (IRI) did not change. In normal subjects given oral triglyceride or galactose followed by intravenous (I.V.) glucose the early-phase response of plasma IRI was enhanced and glucose tolerance improved. In the diabetics, oral triglyceride did not affect insulin release or glucose tolerance after I.V. glucose; oral galactose elicited a slight increase of insulin release without improving glucose tolerance. In the diabetics the rise of plasma IRG after ingestion of triglyceride or galactose was maintained after I.V. glucose. It is concluded that endogenous GIP is insulinotropic and that there is partial resistance to this action in diabetes. The results were compatible with feedback inhibition of GIP secretion by insulin and with the suggestion that the rise of plasma IRG associated with secretion of GIP in diabetics may be due to the glucagonotropic action of this peptide.
Diabetes 1978 Mar
PMID:Effects of ingestion of triglyceride or galactose on secretion of gastric inhibitory polypeptide and on responses to intravenous glucose in normal and diabetic subjects. 64 Feb 38

The effects of repeated injections of 75 U crude cholecystolinin-pancreozymin (CCK-PZ) at increasing plateau glucose concentrations achieved by glucose infusion were studied in 15 controls, 8 chronic pancreatitics and 8 mild maturity onset diabetics. In control subjects CCK-PZ alone caused minor insulin release but proportinally greater secretion with increasing blood glucose concentrations. Chronic pancreatitis patients who had normal responses to intravenous glucose responded normally to the CCK-PZ but at significantly higher plateau glucose levels. Diabetics had no response to IV glucose boluses of 5 g or 10 g, but with glucose infusions of 250-500 mg/min had almost normal insulin responses to CCK-PZ. The responses to CCK-PZ plus glucose were greater than either stimulus alone, indicating an interaction between these and the beta cell. These studies suggest that the gut homone-receptor in the beta cell is intact in maturity onset diabetes and chronic pancreatitis, whether the glucose receptor is normal or defective. The peptide-responsible in the crude CCK-PZ is not secretin, glucagon or gut glucagon, but may be gastric inhibitory polypeptide (GIP) since pure CCK-PZ has no insuli releasing properties.
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PMID:Insulin responses to crude cholecystokinin-pancreozymin in normal subjects, in patients with chronic pancreatitis and patients with mild maturity onset diabetes. 115 Aug 59

Studies were carried out in conscious dogs in which the immunoreactive gastric inhibitory polypeptide (IR-GIP) response to graded doses of oral fat (triglycerides) and glucose was investigated. The IR-GIP response to the doses of triglycerides used was greater and more prolonged than the response to the glucose loads employed. In addition, the relative insulinotropic potencies of exogenous porcine GIP and IR-GIP released by fat as against those released by oral glucose were assessed. When glucose was administered by the oral route, the immunoreactive insulin (IRI) response was magnified above the IRI response to a comparable intravenous glucose load. The serum IRI response to oral glucose was accompanied by a concomitant rise in serum IR-GIP levels, suggesting a causal relationship. IR-GIP released by oral fat was shown to augment the IRI response to an intravenous glucose load, resulting in an improvement of glucose tolerance. Fat-released IR-GIP augmented IRI levels to a lessor degree than either oral glucose or an infusion of porcine GIP.
Diabetes 1975 Dec
PMID:Gastric inhibitory polypeptide. Its physiologic release and insulinotropic action in the dog. 119 9

To investigate the mechanism of oral carbohydrate-stimulated secretion of the two most potent incretin candidates, gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1), we studied the changes in the plasma levels of these peptides in five healthy men after sucrose ingestion with or without pretreatment with an alpha-D-glucosidase inhibitor (AO-128). After sucrose ingestion, plasma levels of GIP peaked at 15 min and remained high up to 120 min. Plasma levels of GLP-1 NT measured with antiserum R1043 (N-terminal specific) tended to decrease gradually and those of GLP-1 CT measured with antiserum R2337 (C-terminal specific) increased. Therefore, estimated plasma levels of tGLP-1 increased markedly within 30 min, then declined slightly over the next 60 min. After treatment with AO-128 (0.6 mg/day) for 1 week, increases in plasma glucose and insulin levels were attenuated and the increase in plasma GIP levels was diminished, while the increase in tGLP-1 levels was sustained much longer. It is concluded that GIP secretion is stimulated by glucose absorption and tGLP-1 secretion by the presence of sucrose in the gut.
Diabetes Res Clin Pract 1992 Mar
PMID:Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion. 157 19

There is a marked difference in insulin secretion between the ob+/ob+ obese mouse and its non-obese littermate. Numerous peptides have been implicated in the modification of postprandial insulin secretion. In this study, the morphological and immunohistochemical studies of the genetically obese mouse (ob+/ob+) pancreata were compared with control littermates. Additionally, the distribution of gastric inhibitory polypeptide, somatostatin, glucagon, and insulin immunoreactive cells was also quantitated. Hyperglycemia and hyperinsulinemia were verified in the obese mice. The control animals had some islets and ductules with mononuclear infiltrations of a possible immune character. The obese individuals had a marked increase in both number and size of the islets of Langerhans compared with lean controls. The insulin immunocytochemical reaction in the obese pancreatic beta-cells was weaker than that of controls, as was the aldehyde-fuchsin reaction. The glucagon, gastric inhibitory polypeptide, and somatostatin containing cells were intermingled with the beta-cells. In contrast, the control animals showed a peripheral localization of these cell types. The morphometric analysis of the obese pancreas showed a decreased proportion of non-beta cells within the islets but not in total pancreatic volume in comparison with controls. The obese mouse also had cavities filled with eosin-stained material among numerous beta-cells. No complete epithelial lining distinguished these formations from the surrounding islet cells. The content of the cavities was not stained by any of the immunocytochemical reactions applied. In conclusion, the pancreatic islets of the ob+/ob+ mouse show marked differences in both morphological and immunocytochemical characteristics if compared with control littermates. These differences in architecture may be related to the eventual development of diabetes mellitus in the ob+/ob+ mouse.
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PMID:A morphological and immunohistochemical investigation of endocrine pancreata from obese ob+/ob+ mice. 167 42

Gastrointestinal hormones with insulinotropic effects, like cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) might tentatively be used in the treatment of non-insulin-dependent diabetes mellitus. We therefore examined the effects of intravenous injection of pharmacological dose levels of CCK-8 (100 and 300 pmol/kg), CCK-33 (100 pmol/kg), GIP (100 pmol/kg), and CCK-8 plus GIP (100 pmol/kg of each) on plasma levels of glucose, insulin, somatostatin, glucagon, and pancreatic polypeptide (PP) in healthy human volunteers. The peptides were given under basal conditions or in combination with a mixed meal. CCK-8, CCK-33, and GIP were all found to increase the basal plasma levels of insulin, somatostatin, and PP; the increases were observed already in samples taken at 2 min after the injection. In contrast, the plasma glucagon levels were unaffected by the peptides. CCK-8, CCK-33, and GIP (100 pmol/kg) all potentiated the meal-induced plasma responses of insulin and PP, whereas plasma levels of glucagon after the meal were not affected. Plasma somatostatin levels after the meal were increased by GIP but not affected by CCK-8 or CCK-33. CCK-8 and GIP together (100 pmol/kg for both) increased plasma levels of insulin, PP and somatostatin as much as each of the peptides given alone, both under basal conditions and after the meal intake. Plasma levels of glucagon were not affected by CCK-8 and GIP together. We conclude that in man, both CCK-8, CCK-33, and GIP moderately stimulate basal and meal related insulin release without any synergistic effects and that the peptides do not inhibit the secretion of glucagon.
Diabetes Res Clin Pract 1991 Sep
PMID:Effects of cholecystokinin (CCK)-8, CCK-33, and gastric inhibitory polypeptide (GIP) on basal and meal-stimulated pancreatic hormone secretion in man. 168 22


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