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The Insulinotropic Effect of Endogenous Gastric Inhibitory Polypeptide in Normal Subjects

Division of Endocrinology and Metabolism, Department of Medicine, Ohio State University Columbus, Ohio 43210

Address reprints to: Ernest L. Mazzaferri, M.D., Division of Endocrinology and Metabolism, Room N-llll, University Hospital, 410 W. 10th Avenue, Columbus, Ohio 43210.

Intravenously administered porcine GIP is insulinotropic in man. This study was designed to investigate the effects of simultaneous fat ingestion, a potent stimulus for GIP release, and intravenous glucose infusion upon endogenous serum GIP and insulin concentrations in normal subjects. Seven normal volunteers were studied on three separate occasions following: a) the ingestion of 67 grams of emulsified com oil, b) constant intravenous infusion of glucose, and c) simultaneous administration of com oil and glucose as in parts (a) and (b) of the study. Serum glucose, insulin (IRI), and GIP concentrations were measured at intervals between 15 and 180 minutes following each stimulus. With corn oil, mean serum GIP concentrations increased from a fasting level of 290 ± 40 (SE) pg/ml to 1936 ± 402 pg/ml at 60 minutes without a significant change in serum IRI or glucose concentrations. The infusion of intravenous glucose alone was associated with no rise in serum GIP levels despite a substantial increase in serum IRI and glucose concentrations. With the combined stimuli, mean serum GIP increased less (P < .05) between 30 and 90 minutes, and total integrated incremental GIP was significantly less (P < .025) than that after corn oil ingestion alone. Following the combined stimuli, incremental insulin levels were higher (P < .05) between 15 and 90 minutes, total integrated incremental insulin was greater (P < .025), and glucose homeostasis was significantly enhanced (P < .05) at 120 and 180 minutes compared with the effects on insulin of glucose infusion alone. We conclude that the potentiation of glucose-stimulated insulin secretion induced by the ingestion of fat is associated with serum GIP levels that are within the insulinotropic range. The augmented secretion of insulin may be mediated partially or completely by endogenous GIP. The lower serum GIP concentrations observed following the combined stimuli suggest a feedback inhibition of GIP release which is perhaps mediated by insulin.

^* Present address: Carswell Air Force Base, Ft. Worth, Texas

Received April 29, 1975.