STIMULATION OF INSULIN SECRETION BY GASTRIC INHIBITORY POLYPEPTIDE IN MAN.¹

Abstract

The effect of very highly purified gastric inhibitory polypeptide (GIP) on insulin secretion in man was tested in normal volunteers. Administration of physiological doses of GIP together with glucose by IV infusion resulted in potentiation of the rise in IRI in the blood and improvement in glucose tolerance. It is concluded that GIP is a potent insulinotropic hormone and probably takes part in physiological potentiation of insulin secretion in response to hyperglycemia during absorption of nutrients from the intestine.Studies with various preparations containing peptldes derived from extracts of porcine duodenojejunal mucosa have suggested that the intestinal hormones secretin and pancreozymin-cholecystokinin (PZ-CCK) are capable of potentiating the rise in insulin in the blood in response to hyperglycemia in man (1). In addition to stimulating insulin secretion the very highly purified preparation of secretin and the relatively crude preparations of PZ-CCK (10% PZ-CCK) used in earlier experiments produced significant improvement in glucose tolerance during intravenous infusions of glucose of two hours duration (2). However, studies in the secretion of rat insulin have shown that the stimulatory effect of 10% PZ-CCK is not reproduced with highly purified ("pure") PZ-CCK (3). Gastric inhibitory polypeptide (GIP), recently identified and characterized as an inhibitor of gastric acid secretion in dogs (4,5), is probably a physiological enterogastrone, and is present in 10% PZ-CCK to the extent of 10-15% by weight (6). Studies with very highly purified GIP have shown that the stimulation of increments in immunoreactive insulin (IRI) in the blood in rats by 10% PZ-CCK can be reproduced by administration of GIP in amounts corresponding to those present in effective doses of 10% PZ-CCK (7). We have therefore examined the effects of very highly purified GIP in man. Submitted July 27, 1973. S.A.R. was In receipt of an award from the New Zealand Diabetes Association. MATERIALS AND METHODSNormal volunteers were tested in the morning after they had fasted overnight. Very highly purified GIP was infused intravenously at the rate of 1 wg/min for a total period of 30 minutes. GIP was prepared according to procedures employed in its identification (A ,5) and was more than 95% pure. Infusates contained human serum albumin 1 mg/ml in normal saline or in glucose 10g%.Glucose was delivered at 0.5 gm/min for 60 min. Insulin and GIP in serum were estimated by radioimmunoassay. In the assay for GIP no interfering crossreaction was detected with glucagon, secretin, vasoactive intestinal polypeptide, gastrin, or pancreozymincholecystokinin (6). Plasma glucose was estimated using glucose oxidase in a Beckman glucose analyzer. RESULTSIn six subjects who received GIP intravenously at the rate used in this study the concentration of GIP in the serum reached a mean peak value of approximately 1 ng/ml by 30 minutes; this concentration is attained in normal subjects after ingestion of glucose (8). The intravenous infusion of GIP in saline at th...

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

“…Thus GLP-1 resembles the biological action of gastric inhibitory polypeptide (GIP), also named glucose-dependent insulinotropic polypeptide, which as the best-established "incretin" candidate stimulates insulin release in a strictly glucose-dependent manner [14][15][16]. Compared with GIP in a similar experimental setting [11], GLP-1 reaches approximately 40% of the maximal insulin response caused by GIP.…”

Incretins, insulin secretion and Type 2 diabetes mellitus

“…The incretin function of GIP was first suggested by one study [19] and was confirmed in detailed clampstudies by another study [20]. Its function has been probed in immunoneutralization studies [21,22] and, more recently, in studies using a fragment, GIP 7-30amide, which turns out to be a GIP receptor antagonist [23], or antibodies to the GIP receptor [24].…”

Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005

“…Around 1973, the peptide gastric inhibitory polypeptide (GIP) had been shown to stimulate insulin secretion [10,11] and was henceforth called glucose-dependent insulinotropic polypeptide, thus preserving the acronym. It was also shown to be likely to function as an important incretin hormone in mimicry experiments [12], in which endogenous hormone concentrations are mimicked by infusion of exogenous hormone.…”