Action Of Gastric Inhibitory Polypeptide Research Articles

Gastric inhibitory polypeptide, insulin, and glucose changes produced by growth hormone, prednisolone, glucagon, insulin, fasting, or diazoxide.

SummaryBecause of the strong augmen-tary action of gastric inhibitory polypeptide (GIP) on insulin secretion, we studied in foxhounds the effect on GIP secretion of several factors known to affect insulin secretion and plasma glucose. Growth hormone infusion decreased plasma GIP, yet increased insulin; no change in plasma glucose was found. Growth hormone inhibited oral glucose-induced increments in plasma GIP and glucose. Prednisolone did not affect levels of GIP or insulin, whether given alone or preceding oral glucose. Diazoxide decreased glucose-induced GIP and insulin secretion, but increased plasma glucose. Fasting for 112 hr decreased GIP but did not decrease the glucose-induced GIP rise. Infusion of glucagon or insulin in amounts sufficient to produce high physiologic or pharmacologic plasma levels did not change GIP concentration, nor did they alter GIP rises with glucose. In conclusion, GIP was not inhibited by insulin or glucagon but was decreased by growth hormone, fasting, or diazoxide. Where...

STIMULATION OF (PRO-)INSULIN BIOSYNTHESIS AND RELEASE BY GASTRIC INHIBITORY POLYPEPTIDE IN ISOLATED ISLETS OF RAT PANCREAS

(Pro-)Insulin biosynthesis ([3H]leucine incorporation) and insulin secretion were studied in collagenase-isolated rat islets incubated for 3 hours at 1 and 2 mg/ml glucose in the presence of gastric inhibitory polypeptide (GIP). GIP augmented [3H]leucine incorporation and release of insulin at both glucose concentrations. In a second series of experiments it was found that an amino acid mixture was without influence on the insulotrophic action of GIP. Combined stimulation of insulin release by GIP and glucagon did not result in higher insulin output than observed in the presence of each substance alone. Thus GIP, in constrast to many other gastrointestinal peptides, however similar to glucagon, enhances not only release but also biosynthesis of insulin. This insulinotrophic action can be observed already at a glucose concentration of 1 mg/ml. The results underline the outstanding role which GIP appears to play in the regulation of beta-cell function.

Immunoassayable Gastric Inhibitory Polypeptide: Investigations into its Role in Carbohydrate Metabolism

Gastric inhibitory polypeptide (GIP) is one of the more recently identified gastrointestinal hormones. Isolated by Brown and co-workers in 1969 (Brown et al., 1969, 1970), it is a member of the glucagon­ secretin family of gastrointestinal hormones and is secreted from mucosal K-cells in the upper part of the small intestine (Solcia et 01., 1978). The major biological actions of GIP were originally thought to be the inhibition of gastrin, pepsin, and gastric acid secretion, and it was these activities which led to its isolation from a crude preparation of porcine cholecystokinin (CCK), which had an uncharacter­ istically high gastric inhibitory activity. However, GIP was subsequently shown to stimulate insulin secretion in the presence of hyperglycaernia (Turner et al., 1974; Brown et al., I975a), and it is this action which is now thought to be the most physiologically relevant. It has long been recognised that hyper­ glycaemia alone cannot entirely account for the rise in plasma insulin observed after the ingestion of glucose (Elrick et al., 1964; Mcintyre et al., 1964). The gastrointestinal hormones gastrin, secretin, and CCK are all able to stimulate insulin secretion under certain conditions and in some species but it is doubtful whether they playa physiological role in influencing insulin secretion in response to oral stimuli (Sum and Preshaw, 1967; Rehfeld and Stadil, 1973; Bloom, 1974). Glucagon-like immunoreactive substances (GLI) of the gut may playa role (Marks and Turner, 1977), but the most likely gastro­ intestinal hormone to occupy such a position is currently thought to be GlP, and therefore the measurement of GIP levels could be of importance in clinical situations where insulin secretion is abnormal.

Interaction of gastric inhibitory polypeptide, glucose, and arginine on insulin and glucagon secretion from the perfused rat pancreas.

Gastric inhibitory polypeptide (GIP) produced an increase in immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) release from the isolated perfused rat pancreas. The magnitude of both effects was shown to be dependent on the prevailing glucose concentration. GIP stimulated IRG release at glucose concentrations less than 5.5 mM and IRI release at glucose levels greater than 5.5 mM. Arginine"stimulated IRG secretion in the presence of low glucose (2.7 mM) was potentiated by GIP. In contrast, GIP augmented arginine-stimulated insulin release only in the presence of arginine concentrations of (less than 20 mM, producing no further increase over a maximal arginine stimulus. The glucagonotropic effect of GIP in the presence of arginine was found to be suppressed by glucose, with the opposite effect observed with insulin release. It was concluded that the endocrine pancreatic action of GIP depends to a great degree on existing levels of modulating nutrients in the blood.

Hypersecretion of Gastric Inhibitory Polypeptide Following Oral Glucose in Diabetes Mellitus

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.

The insulinotropic action of gastric inhibitory polypeptide in the perfused isolated rat pancreas.

Gastric inhibitory polypeptide (GIP) produced a dose-related increase in immunoreactive insulin (IRI) from the perfused isolated rat pancreas. The doses employed were within physiological limits. This effect was glucose-concentration-dependent in that there existed a threshold concentration of glucose above which GIP exerted the insulinotropic action, and that, at a fixed concentration of GIP, increased glucose concentrations stimulated IRI release in more than an additive manner. A biologically active fragment of the GIP molecule was isolated and purified. All criteria have been satisfied that GIP is an insulinotropic hormone.

The effect of somatostatin on release and insulinotropic action of gastric inhibitory polypeptide.

Studies were carried out in conscious dogs in which the effect of intravenous somatostatin on immunoreactive gastric inhibitory polypeptide (IR-GIP) release was investigated. In addition, the inhibitory action of somatostatin on the insulin response to pure porcine GIP was assessed. Intravenous administration of somatostatin resulted in a delayed IR-GIP and immunoreactive insulin (IRI) response to oral glucose. Somatostatin also delayed the IR-GIP response to the ingestion of fat. In both types of experiments, initial depression of IRI levels was followed by a sharp rise in IRI release. Intravenous infusion of somatostatin produced 80% inhibition of the IRI response to pure porcine GIP. It was concluded that somatostatin inhibits the physiological release of IR-GIP and the insulinotropic action of exogenous porcine GIP.

The insulinotropic action of gastric inhibitory polypeptide.

The effect of highly purified gastric inhibitory polypeptide (GIP) on immunoreactive insulin (IRI) secretion in the conscious fasted dog was investigated. Significant increases in IRI release were observed with intravenous administration of three different doses of GIP. These were accompanied by depression in fasting serum-glucose levels. Preliminary studies were undertaken to determine whether this insulinotropic action of GIP could be attributed to a particular segment of the GIP molecule. GIP fragments produced by cleavage with cyanogen bromide and trypsin showed no significant stimulation of IRI release. The possibility that GIP might itself enhance glucose uptake or potentiate insulin-induced glucose uptake was studied with the rat hemidiaphragm preparation. No such effect was observed. In the light of this and other recent work, it is concluded that GIP is a strong candidate for an active principle in the enteroinsular axis.