Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are potent insulinotropic peptides released from the small intestine. To examine their relative contribution to postprandial insulin release, a specific GIP antagonist (ANTGIP) and a GLP-1 antagonist, exendin-(939)-NH₂, were infused into rats after an intragastric glucose meal. In control rats, plasma glucose and insulin levels rose gradually during the first 20 min and then decreased. Exendin-(939)-NH₂ administration inhibited postprandial insulin secretion by 32% at 20 min and concomitantly increased plasma glucose concentrations. In contrast, ANTGIP treatment not only induced a 54% decrease in insulin secretion but also a 15% reduction in plasma glucose levels 20 min after the glucose meal. In vivo studies in rats demonstrated that glucose uptake in the upper small intestine was significantly inhibited by the ANTGIP, an effect that might account for the decrease in plasma glucose levels observed in ANTGIP-treated rats. When the two antagonists were administered to rats concomitantly, no potentiating effect on either insulin release or plasma glucose concentration was detected. Glucose meal-stimulated GLP-1 release was not affected by ANTGIP administration, whereas postprandial glucagon levels were diminished in rats receiving exendin-(939)-NH₂. The results of these studies suggest that GIP and GLP-1 may share a common mechanism in stimulating pancreatic insulin release. Furthermore, the GIP receptor appears to play a role in facilitating glucose uptake in the small intestine.

glucose tolerance test; exendin; glucose-dependent insulinotropic polypeptide antagonist; glucagon

This article has been cited by other articles:

				W. J. Lu, Q. Yang, W. Sun, S. C. Woods, D. D'Alessio, and P. Tso Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1130 - G1138. [Abstract] [Full Text] [PDF]

				D. D'Alessio, W. Lu, W. Sun, S. Zheng, Q. Yang, R. Seeley, S. C. Woods, and P. Tso Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2163 - R2169. [Abstract] [Full Text] [PDF]

				J. Zhou, M. F. A. Livak, M. Bernier, D. C. Muller, O. D. Carlson, D. Elahi, S. Maudsley, and J. M. Egan Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E538 - E547. [Abstract] [Full Text] [PDF]

				F. P. M. O'Harte, K. Hunter, V. A. Gault, N. Irwin, B. D. Green, B. Greer, P. Harriott, C. J. Bailey, and P. R. Flatt Antagonistic effects of two novel GIP analogs, (Hyp3)GIP and (Hyp3)GIPLys16PAL, on the biological actions of GIP and longer-term effects in diabetic ob/ob mice Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1674 - E1682. [Abstract] [Full Text] [PDF]

				M. O. Boylan, L. I. Jepeal, and M. M. Wolfe Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1287 - E1295. [Abstract] [Full Text] [PDF]

				N. Pamir, F. C. Lynn, A. M. J. Buchan, J. Ehses, S. A. Hinke, J. A. Pospisilik, K. Miyawaki, Y. Yamada, Y. Seino, C. H. S. McIntosh, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E931 - E939. [Abstract] [Full Text] [PDF]

				F. C. Lynn, N. Pamir, E. H.C. Ng, C. H.S. McIntosh, T. J. Kieffer, and R. A. Pederson Defective Glucose-Dependent Insulinotropic Polypeptide Receptor Expression in Diabetic Fatty Zucker Rats Diabetes, May 1, 2001; 50(5): 1004 - 1011. [Abstract] [Full Text]

				K. Persson, R. L. Gingerich, S. Nayak, K. Wada, E. Wada, and B. Ahren Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E956 - E962. [Abstract] [Full Text] [PDF]

				K. Filipsson, J. J. Holst, and B. Ahren PACAP contributes to insulin secretion after gastric glucose gavage in mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R424 - R432. [Abstract] [Full Text] [PDF]