Plasma Gastric Inhibitory Polypeptide Research Articles

Effect of intraduodenal and intravenous triglyceride infusions on plasma gastric inhibitory polypeptide and insulin in fetal and neonatal pigs.

The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal and IV triglyceride infusions were measured in 11 late fetal and 10 neonatal pigs. Basal plasma glucose, insulin, and GIP concentrations were lower in fetal than in neonatal pigs. In the fetal pigs, plasma glucose increased slightly during intraduodenal and IV triglyceride infusions, whereas plasma insulin remained unchanged during the tests. No significant changes were observed in plasma GIP concentration following intraduodenal triglyceride infusion in the fetal pigs, but plasma GIP fell during the IV infusion of triglyceride in these pigs (p less than 0.01). In the neonatal pigs, plasma glucose and insulin remained unaffected by intraduodenal and triglyceride infusions. Plasma GIP did not change during the IV triglyceride infusion, but exhibited a paradoxical decline after the intraduodenal triglyceride infusion (p less than 0.05). It is concluded that the GIP-cell response to an oral triglyceride load is suppressed in late fetal and neonatal pigs. The abolished GIP response to oral triglycerides could play a causal role in the inactivity of the enteroinsular axis which is seen in both human and animal neonates.

Fasting portal vein plasma levels of gastric inhibitory polypeptide (GIP) and extractable fasting GIP in the duodenal wall in rats treated with methylprednisolone or alloxan compared with normal controls.

Ten rats were treated with methylprednisolone, another 10 rats with alloxan, and a final 10 control rats with saline. Compared with the controls, the methyl-prednisolone-treated rats had increased fasting levels of serum insulin, blood glucose, and plasma GIP; the alloxan-treated rats had decreased fasting levels of insulin and increased levels of fasting blood glucose and plasma GIP. After removal of the duodenum in the fasting state, the amount of GIP was measured in duodenal tissue specimens after extraction with ice-cold acetic acid, pH 3.0, and with neutralized acetic acid at 95 C. The duodenal content of GIP was 765.5 +/- 60.2 ng/g in the methylprednisolone-treated rats, 897.6 +/-37.3 ng/g in the alloxan-treated rats, and 923.1 +/- 72.9 ng/g in the saline-treated control rats. There were no significant differences in duodenal GIP content between the various groups, nor did the fasting plasma GIP and the amount of duodenal GIP in the individual rats correlate significantly (r=0.147, p less than 0.1). The elevated levels of fasting plasma GIP in the diabetic rats treated with methylprednisolone or alloxan may be due to factors regulating the secretion of GIP rather than to changes in the duodenal content of GIP.

The effects of xylitol on the secretion of insulin and gastric inhibitory polypeptide in man and rats.

Xylitol given by gavage to unadapted rats produced profound diarrhoea and no rise in plasma gastric inhibitory polypeptide (GIP) concentration. In xylitol adapted rats it did not cause diarrhoea but still had no effect upon GIP release in contrast to glucose, which did. In healthy human subjects xylitol taken by mouth in solution as a single 30 g dose produced only a minimal rise in blood glucose and no rise in plasma GIP or insulin concentration. Glucose in similar doses, on the other hand, caused a large rise in all three.

The role of endogenous gastric inhibitory polypeptide in the enteroinsular axis.

In order to elucidate the relationship between the release of gastric inhibitory polypeptide (GIP) and insulin, we compared plasma GIP and insulin concentration responses to meal ingestion in normal subjects and patients with various surgical modifications of the food pathway. Nine patients with Billroth I partial gastrectomy (BI), 7 patients with Billroth II partial gastrectomy (BII), and 6 patients with total gastrectomy (TG) were tested. In BI patients the increase in blood glucose was similar to that in normal subjects, but the response was significantly greater in BII and TG patients. In TG patients blood glucose rose significantly higher in response to a standard meal than in all other groups. In BI patients the mean peak GIP level after meal ingestion was significantly higher than in normal subjects. In BII and TG patients an extremely exaggerated GIP response after the meal was observed. The insulin response to feeding was increased only in the BII and TG patients. Since the insulin response was enhanced only when both the glucose and GIP responses were magnified, we conclude that endogenous GIP is a glucose-dependent insulinotropic factor. In addition, from the fact that meal-stimulated GIP release is most marked in patients with total gastrectomy, we conclude that the direct contact of food with the GIP-producing cells is a strong mechanical or chemical stimulus for GIP release.

Interaction of arginine and gastric inhibitory polypeptide on insulin release in man.

The interrelations of the insulin secretagogues, glucose, arginine (Arg), and gastric inhibitory polypeptide (GIP) were quantified in six normal young men in five sets of experiments with the hyperglycemic clamp technique (125 mg/dl above basal glucose levels for 2 h). After 60 min of intravenous glucose alone, one of the following was added: A) oral glucose (OG) (40 g/m2); B) 15 g.m-2.h-1 Arg infusion; C) 15 g.m-2.h-2 Arg infusion and OG; D) 7.5 g.m-2.h-1 Arg; E) 7.5 g.m-2.h-1 Arg and OG. The clearance rate of Arg was similar for B, C, D, and E. In all experiments, plasma GIP levels were unchanged from the basal level during the 1st h. The increases in plasma GIP levels in experiments C and E were similar to the increase when OG alone was ingested (A). When the stimulatory effect of the secretagogue(s) alone on insulin (IRI) is computed, the increase due to OG (A) and to 7.5 g.m-2.h-1 Arg (D) were similar and additive (A + D approximately equal to E). However, the stimulatory effect of 15 g.m-2.h-1 Arg + OG (C) on IRI was not significantly greater than 15 g.m-2.h-1 alone (B). The 15 and 7.5 g.m-2.h-1 Arg infusion produced different patterns of insulin and glucagon secretions. At the lower dose, the response of both hormones to Arg decreased with time. Arg and GIP act through a similar and possibly common mechanism on the beta-cell. However, only Arg was found to be alpha-cytotropic. GIP does not appear to influence the metabolic clearance of Arg. The dose-response relationships to Arg of the beta- and alpha-cell appear similar.

Preparation of 125I-labeled gastric inhibitory polypeptide, using water-insoluble 1,2,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril (Iodo-gen) as the oxidizing agent.

The preparation and evaluation of a 125I-labeled gastric inhibitory polypeptide (GIP) by means of a modified Iodo-gen method are described. The portal vein fasting plasma GIP concentration was determined in 6 groups of rats with 10 rats in each group. In three of the groups, three separately prepared Iodo-gen tracers were used in the radioimmunoassay, and in the three other groups three separately prepared chloramine-T tracers were used. The mean fasting portal vein plasma GIP concentrations in the three groups were 45.0 +/- 5.0, 41.9 +/- 3.9, and 39.6 +/- 2.7 pmol/l, respectively, with the Iodo-gen tracers and 80.3 +/- 4.6, 78.4 +/- 5.4, and 85.7 +/- 3.7 pmol/l with the chloramine-T tracers. The values obtained in each of the groups with the Iodo-gen tracers were significantly lower than those obtained in each of the groups with the chloramine-T tracers. This may be due to a better preserved immunoreactivity of the Iodo-gen tracer than of the chloramine-T tracer. The explanation of this may be the water insolubility of Iodo-gen, which may prevent oxidation of easily oxidized residues of the peptide during the radioiodination procedure.

Gastric inhibitory polypeptide and insulin release in response to oral and intravenous glucose in coeliac disease.

Eight patients with biopsy-verified coeliac disease were investigated after remission on a gluten-free diet. A 50-g oral glucose load (OGTT) and an intravenous glucose infusion (IVGI) giving the same plasma glucose profile as the OGTT were carried out. The relation between gastric inhibitory polypeptide (GIP) plasma levels after oral glucose and the insulin release during OGTT and IVGI were studied. Plasma GIP concentration in the fasting state and the increase in plasma GIP during OGTT were significantly lower than in a group of eight healthy volunteers. However, the insulin potentiation during OGTT, the incretin effect, was normal. The results indicate the existence of other incretins than GIP. These are probably released from the distal small bowel in patients with coeliac disease.

Beta-adrenergic stimulation and blockade of the release of gastric inhibitory polypeptide and insulin in man.

The effect of beta-adrenergic receptor stimulation with isoproterenol and blockade with propranolol on the release of gastric inhibitory polypeptide (GIP) and insulin was investigated in seven healthy volunteers. In the control experiment, the concentration of GIP in plasma increased from 30.1 (18.9-58.8) to 77.2 (44.2-121) pM after 30 g oral glucose. The concentration of insulin in serum increased from 7 (4-12) to 34 (13-76) mU/l. During infusion with isoproterenol, plasma GIP increased from 29.9 (25.7-39.1) to 47.1 (37.2-83.8) pM and insulin from 9 (5-15) to 37 (16-72) mU/l before oral glucose. After oral glucose, further increases of GIP to 111 (68.8-171) pM and of insulin to 103 (33-131) mU/l were observed. When propranolol was given in addition during this beta-receptor stimulation, plasma GIP after glucose increased to 82.2 (49.7-145) pM and serum insulin to 61 (9-133) mU/l. An isoproterenol-induced increase in the concentration of GIP and insulin was thus counteracted by propranolol. This strongly indicates that not only the insulin release but also the entero-insular axis as a total is influenced by beta-adrenergic mechanisms.

The effect of Metamucil on postprandial blood glucose and plasma gastric inhibitory peptide in insulin-dependent diabetics.

ABSTRACT. Postprandial hyperglycemia was significantly (p<0.05) reduced during administration of the fibre supplement Metamucil in nine insulin‐dependent diabetics. A similar but less pronounced effect was also found on the plasma gastric inhibitory polypeptide secretion. Six subjects noted an increased frequency of hypoglycemic episodes, and reductions in insulin dosage might have been necessary if the experiment had continued longer.

The effect of calcium on the release of gastric inhibitory polypeptide (GIP) - with reference to the release of GIP in patients with hyperparathyroidism (author's transl)

Plasma gastric inhibitory polypeptide (GIP), insulin, glucagon concentrations and blood glucose levels in response to the ingestion of 100 g glucose were measured in 5 patients with hyperparathyroidism in order to elucidate the effect of hypercalcemia on the release of these hormones. In addition, the effect of acute hypercalcemia on the release of these hormones in response to glucose ingestion was investigated in normal subjects. Fasting plasma GIP concentration in patients with hyperparathyroidism was significantly greater than the value in seventeen normal subjects. Significantly higher responses of plasma GIP and insulin were observed after the glucose ingestion in the patients with hyperparathyroidism as compared with the values in the normal subjects, and integrated GIP and insulin responses to the glucose ingestion for 120 min in the patients with hyperparathyroidism were significantly greater than the values in the normal subjects. On the other hand, plasma glucagon concentration after the glucose ingestion in the patients with hyperparathyroidism remained unchanged, although plasma glucagon concentrations after the glucose ingestion decreased significantly from the basal value in the normal subjects. Blood glucose levels after the glucose ingestion in two groups increased significantly from the basal value in the same manner. In nine normal subjects calcium infusion (4 mg/kg bolus injection followed by continuous infusion of 4 mg/kg/hr for 3 hr) caused a significantly high concentration of plasma calcium (11.5 approximately 13.0 mg/dl) from the basal value. Significantly higher responses of plasma GIP and insulin to the glucose ingestion were observed during calcium infusion as compared with the values during saline infusion. On the other hand, plasma glucagon concentration after the glucose ingestion was not significantly changed during calcium infusion in contrast with a significant decrease of plasma glucagon after the glucose ingestion during saline infusion. Consequently, calcium was considered to play a major part in the release of GIP and insulin. The characteristic response of plasma glucagon during calcium infusion was considered, at least in part, to protect the hypoglycemia caused by hyperinsulinemia.

Effect of gastrin on fasting and postprandial plasma GIP release in man.

In order to evaluate the mechanism behind the augmented postprandial gastric inhibitory polypeptide (GIP) release seen in patients with achlorhydria and hypergastrinemia, 8 healthy subjects were given a liquid test meal on three different days. On 1 day the meal was preceded by ranitidine (H2 receptor antagonist) to block the gastric H+ secretion. On another day the meal was also preceded by ranitidine, but on this occasion gastrin was infused intravenously during the first hour in order to induce hypergastrinemia. On a third day the meal was given along to serve as a control. Finally, 6 healthy fasting subjects were given a 1-hour intravenous infusion of gastrin after pretreatment with ranitidine. Plasma GIP responses after the meal on the days with ranitidine alone or together with the gastrin infusion did not differ significantly from that found on the control day. When gastrin was infused in the fasting state, no effect was seen on the basal GIP levels. Thus, neither exogenous gastrin nor achlorhydria seems to affect the plasma GIP release, and it appears more likely that a rapid gastric emptying rate can account for the augmented GIP response found in achlorhydric patients.

The response of plasma gastric-inhibitory polypeptide (GIP) to slow and fast glucose ingestion in Billroth II resected patients and normal controls

Eight Billroth II resected patients and 8 normal controls were given two oral glucose loads, one ingested within 2 min, and the other ingested slowly over 80 min. In the Billroth II resected group, the integrated plasma GIP release was significantly higher after the fast than after the slow glucose ingestion. In this group the integrated plasma GIP release was also significantly higher than in the control group, but only after the fast glucose ingestion. These findings indicate that the rate of glucose delivery into the intestine may be of importance in the plasma GIP response to oral glucose.

Gastric inhibitory polypeptide release into the portal vein in response to intraduodenal glucose loads in anesthetized rats.

Gastric inhibitory polypeptide (GIP) release into the portal vein in response to duodenal instillation of glucose in doses of 0.695, 1.39, 2.78 and 5.56 mmol/kg body weight was studied in an acute condition in male Wistar rats. A rapid, dose-dependent, and significant rise in portal vein plasma GIP was found in response to increasing duodenal glucose loads, which could be described by Michaelis-Menten kinetics. It is suggested that the glucose-induced GIP release into the portal vein mainly is effected first after glucose has gained access inside the mucosal cells.

Failure of gastric inhibitory polypeptide to inhibit pentagastrin-stimulated acid secretion in vagotomized human subjects.

Five vagotomized male subjects were given graded doses of pentagastrin without and with a background infusion of 2 microgram/kg/hr of gastric inhibitory polypeptide (GIP). An insulin infusion test (0.1 units/kg/hr) showed that the vagotomies were complete. GIP infusion failed to inhibit pentagastrin-stimulated acid and pepsin secretion even though plasma GIP concentration reached a plateau much higher than that measured after ingestion of a meal. We conclude that GIP does not inhibit pentagastrin-stimulated gastric acid secretion in vagotomized human subjects.

GIP and Insulin Responses to Oral Glucose in Coeliac Patients before and after Treatment

The responses of plasma gastric inhibitory polypeptide (GIP) and insulin to oral glucose were studied in five patients with untreated coeliac disease. These patients were restudied after one year on a gluten-free diet. In the untreated patients, the blood glucose, serum insulin, and GIP levels were significantly lower than in the controls. After gluten withdrawal there was an improvement towards normality in the responses of blood glucose, serum insulin, and GIP. The results show that untreated coeliac disease is associated with abnormalities of intestinal and pancreatic hormone secretion and that these abnormalities are improved by gluten withdrawal.

Hypersecretion of gastric inhibitory polypeptide induced by glucose ingestion in diabetes mellitus.

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.

Diets rich in natural fibre improve carbohydrate tolerance in maturity-onset, non-insulin dependent diabetics

The influence of low and high fibre diets upon carbohydrate tolerance was examined in five maturity-onset, non-insulin dependent diabetics. After 14 days on a diet rich in natural fibre (30 g/day), the subjects consumed a high fibre (13 g) test meal. They then ate a low fibre diet (10 g/day) followed by a low fibre (1 g) test meal. Mean basal plasma glucose concentrations were similar after both fibre diets; however, both mean basal plasma insulin and gastric inhibitory polypeptide (GIP) were significantly lower after the high fibre diet. After the high fibre test meal, significantly lower mean plasma glucose, insulin and GIP concentrations were measured. This study is the first study to demonstrate the ability of an institutionally supervised diet of natural foodstuffs rich in fibre to improve carbohydrate tolerance in maturity-onset, non-insulin dependent diabetics. This findings is relevant to the dietary management of diabetics.

The association between plasma GIP and insulin after oral glucose.

The correlation between the peripheral concentrations of gastric inhibitory polypeptide (GIP), insulin, and glucose has not previously been quantified. This paper describes the association among the peripheral concentrations of GIP, insulin and glucose during 50-g oral glucose tolerance tests (OGTT) in healthy volunteers and in patients with gastrointestinal disorders, obesity, and uremia. It was found that the correlation between insulin/glucose and plasma GIP concentrations during an OGTT can be expressed by the equation: log y = log a + bx, where y = [insulin]/[glucose], and x is the plasma GIP concentration. This empirical correlation between [insulin]/[glucose] and [GIP] reduces the plasma parameters measured during OGTT to a simple relationship. It may prove valuable in the analysis of differences in the relationship glucose-insulin-GIP between groups of subjects and in the description of alterations in glucose homeostasis longitudinally in individuals undergoing therapy.

Gastric inhibitory polypeptide (GIP) and insulin release after small-bowel resection in man.

Fifteen patients in whom various parts of the small intestine had been resected because of Crohn's disease or mesenteric thrombosis and 10 healthy volunteers were studied. A 50-g oral glucose load (OGTT) and an intravenous glucose infusion giving the same plasma glucose profile as the OGTT were carried out to study (a) the relation between the plasma gastric inhibitory polypeptide (GIP) levels after oral glucose and the length and nature of the intestinal residues and (b) the importance of endogenous GIP as an incretin in man. The magnitude of the increase in plasma GIP after oral glucose load was positively correlated to the length of residual jejunum. The incretin effect was positively correlated to the length of residual intestine. Patients with preserved ileal residues had larger incretin effects than patients with less than 150 cm jejunal residues and no ileal residues, although the integrated increases in plasma GIP after oral glucose were equal. Compared with healthy volunteers, the patients with more than 150 cm residual jejunum had significantly higher increases in plasma GIP and normal incretin effects. The GIP release and the incretin effect in patients with preserved ileal residues were normal. The incretin effect of the patients with less than 150 cm jejunum was significantly subnormal in spite of a normal GIP release. These findings indicate that the upper intestine releases GIP after oral glucose and that other as yet unknown intestinal hormonal factors act as incretins in concert with GIP.

Diurnal variation of plasma gastric inhibitory polypeptide in man.

Plasma gastric inhibitory polypeptide (GIP) was studied for 24 h in six healthy, young men who ate four meals and performed their usual physical activities. Plasma GIP peaked after each meal and stayed significantly elevated from the peak after breakfast till late evening.