Serum Immunoreactive Gastric Inhibitory Polypeptide Research Articles

Effects of gastric inhibitory polypeptide on leucine- and arginine-stimulated insulin release.

Insulin release stimulated by single amino acids, with and without gastric inhibitory polypeptide (GIP), was studied in vivo in anesthetized rats and in vitro in collagenase-digested isolated rat pancreatic islets. Insulin release in vivo during a 15-min intravenous infusion of leucine (0.97 mM) or arginine (0.97 mM) with GIP (17 ng/min) was greater than with infusion of either amino acid or GIP alone. Serum immunoreactive GIP was in the physiological range, and serum glucose showed no significant change in these studies. In contrast, insulin release did not occur with valine infused alone or with GIP. Insulin release in vitro by isolated islets was greater during a 45-min incubation period with leucine (5-20 mM) or arginine (20 mM) plus GIP (10 ng to 10 micrograms/ml) than with either amino acid alone. This effect that occurred in the absence of glucose could not be demonstrated with low concentrations of leucine (1.5 mM) or with 20 mM valine. In vitro insulin release during paired perfusion studies of isolated islets was greater with leucine (20 mM) plus GIP (50 ng/min) than with leucine alone, and augmentation of insulin release by GIP was demonstrable in both the early and late phases of insulin release. From these results it is concluded that insulin release is greater, both in vivo and in vitro, after leucine or arginine plus GIP than with either amino acid or GIP alone. This effect appears to be specific for the insulinotropic amino acids tested, does not appear to be glucose dependent, and can be demonstrated in both the early and late phases of insulin release.

Effect of exogenous insulin on fasting serum levels of gastric inhibitory polypeptide (GIP) in juvenile diabetes.

The effect of insulin on fasting levels of immunoreactive gastric inhibitory polypeptide (IR-GIP) has been examined in insulin-dependent, juvenile-type diabetics who were well-controlled with two doses of an intermediate insulin. After withdrawal of the evening insulin injection the fasting blood glucose and serum IR-GIP levels were elevated and decreased significantly following intravenous insulin towards normal values. There was a significant positive correlation between levels of blood glucose and serum IR-GIP before and during insulin application. It is suggested that fasting serum GIP levels increase in case of insulin deficiency because basal GIP secretion is suppressed by normal insulin levels.

The importance of triglyceride hydrolysis for the release of gastric inhibitory polypeptide

Gastric inhibitory polypeptide is released from the small intestine after the ingestion of fat, but it is not known if triglyceride itself or one of its hydrolytic products is the stimulus to gastric inhibitory polypeptide secretion. Children with cystic fibrosis and defective fat lipolysis were studied to help define the exact stimulus to gastric inhibitory polypeptide secretion. Pancreatic enzyme therapy was withheld from the children with cystic fibrosis during these tests. Ten normal children and 10 children with cystic fibrosis each ingested corn oil and serum immunoreactive gastric inhibitory polypeptide measured. The normal children had a 10-fold increase in serum gastric inhibitory polypeptide levels after the triglyceride, but no increase in immunoreactive gastric inhibitory polypeptide occurred in the children with cystic fibrosis. When three of the children with cystic fibrosis received their pancreatic enzymes and then ingested the triglyceride, gastric inhibitory polypeptide values increased 10-fold. To assess the relative importance of the products of triglyceride hydrolysis and the chain length of the component fatty acids, 6 normal adults consumed, on separate days, 40 mmol of corn oil, medium-chain triglycerides, long-chain fatty acids, or glycerol. Long-chain fatty acids caused a fourfold increase and triglyceride a 12-fold increase in gastric inhibitory polypeptide levels. There was no increase after medium-chain triglyceride or glycerol. This indicates that long-chain fatty acids—the end product of triglyceride hydrolysis—are a stimulus to gastric inhibitory polypeptide secretion; that this release is apparently proportional to the quantity of long-chain fatty acid present; and that hydrolysis of triglyceride is required before gastric inhibitory polypeptide release can normally occur after fat ingestion.

Gastric inhibitory polypeptide (GIP) is not the primary mediator of the enterogastrone action of fat in the dog

We compared the inhibition of food-stimulated gastric acid secretion and changes in serum concentrations of immunoreactive gastric inhibitory polypeptide and gastrin caused by: (a) duodenal perfusion of oleic acid, and (b) intravenous infusion of pure, natural, porcine gastric inhibitory polypeptide in dogs with gastric fistula and pancreatic fistula. A rate of duodenal perfusion of oleic acid (12 ml/hr) which gave near maximal pancreatic protein response was chosen. This dose of oleic acid caused complete suppression of acid response to a meal of liver extract (300 ml of a 15% solution) while elevating serum immunoreactive gastric inhibitory polypeptide modestly. By contrast, intravenous administration of gastric inhibitory polypeptide that raised serum immunoreactive gastric inhibitory polypeptide several fold caused only 40% inhibition of acid response to the same meal. Other effects of duodenal perfusion of oleic acid were exaggeration of pancreatic protein secretion and significant inhibition of gastrin release in response to the meal. Exogenous administration of gastric inhibitory polypeptide, on the other hand, was without significant effect on these responses. These results suggest that, in the innervated dog stomach, the enterogastrone action of fat is not primarily mediated by gastric inhibitory polypeptide.

Inhibition of gastric inhibitory polypeptide (GIP) release by insulin and glucose in juvenile diabetes.

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.

Effect of atropine on glucose-stimulated gastric inhibitory polypeptide.

Gastrointestinal augmentation of insulin secretion observed in response to glucose ingestion may be largely mediated by gastric inhibitory polypeptide (GIP). Since the enteric signal potentiating insulin secretion is blunted by atropine, we studied the effects of this drug on glucose-stimulated GIP secretion in normal subjects. Eight individuals, studied on two occasions, were given intraduodenal glucose (75 gm. over 60 minutes) by perfusion tube, on one occasion with intravenous atropine (15 μg. per kilogram bolus followed by 17 μg. per minute for 60 minutes) and on another occasion with intravenous saline (control). Comparing the results of atropine and control studies, mean serum immunoreactive GIP (IRGIP) was significantly lower at 5 and 15 minutes (444 ± 82 vs. 277 ± 44, p < 0.05 and 1,072 ± 151 vs. 427 ± 74 pg./ml., p < 0.02 at 5 and 15 minutes, respectively), and the integrated incremental area under the 120-minute curve was significantly less (62,170 ± 11,880 vs. 91,820 ± 14,200 pg. ·minute·ml.−1 p < 0.05) with atropine. Serum IRI levels were also significantly lower during the atropine studies (28 ± 8 vs. 14 ± 2, p < 0.05, 54 ± 7 vs. 25 ± 5, p < 0.02, 62 ± 8 vs. 36 ± 7 μU. per milliliter, p < 0.05, at 15, 30, and 45 minutes, respectively). The integrated incremental area under the IRGIP curve was reduced about 33 per cent, while the area under the IRI curve was reduced about 45 per cent by atropine. In a second group of similar experiments substituting d-xylose for glucose, the effect of atropine on d-xylose absorption was studied in normal subjects. Atropine did not alter d-xylose absorption during the first hour, but significantly enhanced its absorption during the second hour, as compared with control studies. We conclude that atropine blunts the rise in serum IRGIP normally stimulated by intestinal glucose perfusion, which is probably a direct effect of the drug on the gastrointestinal tract, as opposed to an effect mediated by inhibition of glucose absorption. These observations are consistent with the hypothesis that GIP is the enteric signal potentiating insulin secretion that is attenuated by atropine.

Gastric inhibitory polypeptide (GIP) and insulin in obesity: Increased response to stimulation and defective feedback control of serum levels

To investigate the possibility that an abnormality of the entero-insular axis is responsible for the hyperinsulinaemia of obesity, serum immunoreactive gastric inhibitory polypeptide (IR-GIP) and insulin (IRI) were measured after the ingestion of a liquid mixed test meal, glucose or fat, in normal weight and obese subjects. The latter were divided into a group with normal oral glucose tolerance (nOGT) and a group with pathological glucose tolerance (pOGT). Fasting levels of IR-GIP were significantly elevated in the obese group with pOGT. After the mixed meal the overweight subjects showed a significantly greater response of IR-GIP than the controls, with highest levels in the pOGT group. Simultaneously, the IRI response was significantly greater in the obese subjects than in the controls. The increases of IR-GIP and IRI after an oral load of 100 g glucose were normal in the obese subjects, but showed a significantly greater integrated response in the obese patients with pOGT. The ingestion of 100 g fat induced no IRI release but a significantly greater release of IR-GIP in the obese subjects, irrespective of their glucose tolerance. It is concluded that fat is a stronger releaser of IR-GIP than glucose. The effect of a combined load of glucose (30 g) and fat (100 g) was also compared in obese and normal weight subjects with the effect of either alone. Fat but not glucose released significantly more IR-GIP in obese subjects. In normal weight controls, but not in obese subjects, the IR-GIP release after fat plus glucose became significantly smaller than after fat alone. Since only the combined ingestion of glucose and fat and not fat alone releases insulin it is suggested that endogenous insulin inhibits GIP release and that this feedback control between insulin and GIP is defective in patients with obesity.

Serum Gastric Inhibitory Polypeptide (GIP) in Duodenal Ulcer Disease: Relationship to Glucose Tolerance, Insulin, and Gastrin Release

Serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG), and insulin (IRI) were estimated in 41 normal weight patients with duodenal ulcer (DU) and 25 age-matched controls in response to a high calorie liquid test meal. 28 out of 41 DU patients had a hyperglycaemic glucose response during the test meal, and 15 had a pathological oral glucose tolerance test. Fasting and food-stimulated IR-GIP and IRG levels were significantly elevated in the DU patients. Serum IRI also increased to significantly higher levels in DU patients after the test meal. The degree of the greater hormone response was dependent on the glucose increase after the test meal in the case of insulin and GIP, but not in the case of gastrin. It is concluded: firstly, that a faster glucose absorption (possibly due to rapid initial gastric emptying or increased intestinal motility) is responsible for the high and short-lasting glucose peak and the increased GIP and insulin secretion; secondly, that the GIP response could well be causally related to the insulin response; thirdly, that hyposcretion of GIP is ruled out as a possible factor in the pathogenesis of gastric acid hypersecretion of duodenal ulcer patients.

Renal effects on serum gastric inhibitory polypeptide (GIP)

Fasting and meal-stimulated serum immunoreactive gastric inhibitory polypeptide (GIP) concentrations were measured in normal subjects and in uremic patients undergoing chronic hemodialysis. Mean fasting GIP was higher in the uremic patients (1006 ± 145 (SE) pg/ml) than in the normal control subjects (132 ± 31 pg/ml, p < 0.001). Also, postcibal absolute and incremental serum GIP concentrations between 15 and 180 min were greater ( p < 0.05) in the uremic patients than in the control subjects; in the former they failed to return to fasting levels 180 min after the meal. In a second study, using anesthetized normal dogs, simultaneous renal arterial and venous serum GIP concentrations were measured during an intraduodenal perfusion of glucose. The renal arterial-venous (A-V) GIP gradient became greater as serum arterial GIP concentrations increased. The correlation between renal A-V GIP gradient and renal arterial GIP concentration was quite good ( r = 0.85), with a 39% maximum mean A-V reduction in serum GIP concentrations observed across the kidney. This large renal A-V GIP gradient observed under nonsteady conditions suggests that the kidney may be an important site for the removal of GIP from the circulation. Thus, the higher than normal fasting and stimulated serum GIP concentrations observed in uremic patients can be attributed, at least in part, to a loss of the renal extraction mechanism for GIP.

Lowering of fasting and food stimulated serum immunoreactive gastric inhibitory polypeptide (GIP) by glucagon.

The effect of intravenous glucagon infusion on serum levels of immunoreactive GIP (IR-GIP), insulin (IRI), gastrin (IRG), and on blood glucose has been investigated in six healthy volunteers in the fasting state and during ingestion of a mixed standard meal. Glucagon (500 ng/kg/min) lowered significantly serum levels of IR-GIP and IRG below the fasting values and increased the levels of IRI and blood glucose. Glucagon (50 ng/kg/min) infused 30 minutes before and continued 90 minutes after ingestion of a test meal abolished the IR-GIP response, suppressed significantly the IRG response, and left the IRI response unchanged. The same glucagon dose infused 60 minutes after ingestion of the test meal decreased significantly the raised levels of IR-GIP and IRG to fasting levels without changing IRI values. It is concluded that exogenous glucagon inhibits Gip release at the level of the GIP-producing cells.

Gastric inhibitory polypeptide (GIP), gastrin and insulin: response to test meal in coeliac disease and after duodeno-pancreatectomy.

The response of serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG) and insulin (IRI) to a mixed standard meal was measured in 15 controls, 6 patients with coeliac disease, 26 patients with chronic pancreatitis and partial duodenopancreatectomy (Whipple's procedure). Serum levels of IR-GIP, IRG and IRI were significantly reduced in patients with coeliac disease. The serum glucose increase was significantly smaller only during the first hour after the meal. Since small intestinal GIP- and G-cells are situated mainly in the glands of duodenal and jejunal mucosa their absolute number is not significantly reduced in coeliac disease. It is suggested that the release of IR-GIP and duodenal IRG is influenced by the rate of absorption of nutrients. In patients with chronic pancreatitis the IR-GIP release is significantly greater than in controls, the IRG release normal and the IRI response delayed. After Whipple's procedure the IR-GIP response is increased significantly while the IRG secretion is abolished. This demonstrates that the duodenum is not necessary for GIP release and that pancreatic and jejunal gastrin are without clinical significance.