Journal of Clinical Endocrinology & Metabolism, Vol 69, 654-662, Copyright © 1989 by Endocrine Society

ARTICLES

Insulinotropic properties of synthetic human gastric inhibitory polypeptide in man: interactions with glucose, phenylalanine, and cholecystokinin-8

M Nauck, WE Schmidt, R Ebert, J Strietzel, P Cantor, G Hoffmann and W Creutzfeldt
Department of Medicine, Georg-August-University Gottingen, West Germany.

The quantitative contribution of glucose-dependent insulinotropic polypeptide [gastric inhibitory polypeptide (GIP)] to the incretin effect after oral glucose (augmentation of insulin secretion over the degree that is explained by the glycemic rise) is not known. Therefore, hyperglycemic clamp experiments (8 mmol/L, corresponding to postprandial glucose concentrations) were performed in healthy volunteers, and synthetic human GIP was infused for 60 min at a rate (approximately 1.3 pmol/kg.min) that results in plasma GIP concentrations similar to those occurring after oral glucose loads of 75 g. The MCR for exogenous GIP was approximately 6 mL/kg.min; the decay after ceasing infusion was exponential with a t1/2 of about 18 min, and the resulting volume of distribution was about 140 mL/kg. At euglycemic (basal) plasma glucose concentrations (5.0 mmol/L) similar values were found. Insulin secretion was stimulated by hyperglycemia alone, but was greatly (2.3-fold based on C-peptide) potentiated by GIP infusions (P less than or equal to 0.001 for integrated incremental values). When integrated incremental responses over 120 min of GIP, immunoreactive insulin, and immunoreactive C-peptide were compared after oral glucose and during GIP infusions, no significant differences were found. Peak glucose concentrations after oral glucose (7.6 +/- 0.6 mmol/L) were similar to mean plasma glucose values during clamp experiments (8.2 +/- 0.1 mmol/L; P = 0.124). However, mean glucose concentrations after oral glucose were lower (6.0 +/- 0.3 mmol/L; P = 0.0004). Additional infusion of sulfated cholecystokinin-8 (25 pmol/kg.h) or the amino acid phenylalanine (1.7 mumol/kg.min) did not further stimulate insulin secretion and had no influence on the pharmacokinetics of exogenous GIP. It is concluded that human synthetic GIP is insulinotropic in man and that this activity may well explain a substantial part of the incretin effect after oral glucose. There is no interaction with cholecystokinin or phenylalanine in concentrations found after mixed meals.

This article has been cited by other articles:

				J. J. Holst The Physiology of Glucagon-like Peptide 1 Physiol Rev, October 1, 2007; 87(4): 1409 - 1439. [Abstract] [Full Text] [PDF]

				R K. Campbell Rationale for Dipeptidyl Peptidase 4 Inhibitors: A New Class of Oral Agents for the Treatment of Type 2 Diabetes Mellitus Ann. Pharmacother., January 1, 2007; 41(1): 51 - 60. [Abstract] [Full Text] [PDF]

				J. J. Holst and C. Orskov The Incretin Approach for Diabetes Treatment: Modulation of Islet Hormone Release by GLP-1 Agonism Diabetes, December 1, 2004; 53(suppl_3): S197 - S204. [Abstract] [Full Text] [PDF]

				J. J. Holst and J. Gromada Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E199 - E206. [Abstract] [Full Text] [PDF]

				J. J. Meier, M. A. Nauck, D. Kranz, J. J. Holst, C. F. Deacon, D. Gaeckler, W. E. Schmidt, and B. Gallwitz Secretion, Degradation, and Elimination of Glucagon-Like Peptide 1 and Gastric Inhibitory Polypeptide in Patients with Chronic Renal Insufficiency and Healthy Control Subjects Diabetes, March 1, 2004; 53(3): 654 - 662. [Abstract] [Full Text] [PDF]

				S. A. Hinke, R. W. Gelling, R. A. Pederson, S. Manhart, C. Nian, H.-U. Demuth, and C. H.S. McIntosh Dipeptidyl Peptidase IV-Resistant [D-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats Diabetes, March 1, 2002; 51(3): 652 - 661. [Abstract] [Full Text] [PDF]

				C. F. Deacon, M. A. Nauck, J. Meier, K. Hücking, and J. J. Holst Degradation of Endogenous and Exogenous Gastric Inhibitory Polypeptide in Healthy and in Type 2 Diabetic Subjects as Revealed Using a New Assay for the Intact Peptide J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3575 - 3581. [Abstract] [Full Text]

				J. T. Lewis, B. Dayanandan, J. F. Habener, and T. J. Kieffer Glucose-Dependent Insulinotropic Polypeptide Confers Early Phase Insulin Release to Oral Glucose in Rats: Demonstration by a Receptor Antagonist Endocrinology, October 1, 2000; 141(10): 3710 - 3716. [Abstract] [Full Text] [PDF]

				C.-C. Tseng, X.-Y. Zhang, and M. M. Wolfe Effect of GIP and GLP-1 antagonists on insulin release in the rat Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1049 - E1054. [Abstract] [Full Text] [PDF]