This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fritsche, A. Articles by Stumvoll, M. Search for Related Content PubMed PubMed Citation Articles by Fritsche, A. Articles by Stumvoll, M.

The Prevalent Gly1057Asp Polymorphism in the Insulin Receptor Substrate-2 Gene Is Not Associated with Impaired Insulin Secretion

Medizinische Klinik, Abteilung für Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universität, Tübingen, Germany

Address all correspondence and requests for reprints to: Dr. Michael Stumvoll, Medizinische Universitätsklinik, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. E-mail: Michael.Stumvoll{at}med.uni-tuebingen.de

Abstract

Disruption of the insulin receptor substrate-2 was shown to cause type 2 diabetes in mice. This could be largely attributed to abnormal ß-cell development. In humans, a prevalent polymorphism in insulin receptor substrate-2 (Gly1057Asp) was not found be associated with type 2 diabetes in linkage and association studies. We tested the hypothesis that an extreme challenge of the ß cell might reveal subtle abnormalities in carriers of this polymorphism undetected by conventional insulin secretion tests. Therefore, in addition to assessing ß-cell function by oral glucose tolerance testing (n = 318, normal glucose tolerance), we measured the secretory response to maximal stimulation by hyperglycemia (10 mM), glucagon-like peptide-1, and arginine administered in an additive fashion (n = 77, nondiabetic). The allelic frequency of the Asp allele was 37%. Neither the ß-cell function indices from the oral glucose tolerance test nor the secretory response during the hyperglycemic clamp differed measurably between carriers and controls. Moreover, maximal plasma C-peptide concentrations in response to the combined glucose, glucagon-like peptide-1, and arginine stimulus was not different between Gly/Gly (10,745 ± 1,186 pmol/liter) and X/Asp (10,800 ± 490 pmol/liter, P = 0.99). In conclusion, our findings strongly suggest that the Gly1057Asp polymorphism in insulin receptor substrate-2 is not associated with ß-cell dysfunction. The normal maximal insulin secretory response makes it unlikely that this common polymorphism results in abnormal ß-cell development.

This article has been cited by other articles:

				W.-D. Li, C. Dong, D. Li, C. Garrigan, and R. A. Price A genome scan for serum triglyceride in obese nuclear families J. Lipid Res., March 1, 2005; 46(3): 432 - 438. [Abstract] [Full Text] [PDF]

				N. Stefan, P. Kovacs, M. Stumvoll, R. L. Hanson, A. Lehn-Stefan, P. A. Permana, L. J. Baier, P. A. Tataranni, K. Silver, and C. Bogardus Metabolic Effects of the Gly1057Asp Polymorphism in IRS-2 and Interactions With Obesity Diabetes, June 1, 2003; 52(6): 1544 - 1550. [Abstract] [Full Text] [PDF]

				O. Tschritter, A. Fritsche, F. Shirkavand, F. Machicao, H. Haring, and M. Stumvoll Assessing the Shape of the Glucose Curve During an Oral Glucose Tolerance Test Diabetes Care, April 1, 2003; 26(4): 1026 - 1033. [Abstract] [Full Text] [PDF]

				R. C. Bonadonna, M. Stumvoll, A. Fritsche, M. Muggeo, H. Haring, E. Bonora, and T. W. van Haeften Altered Homeostatic Adaptation of First- and Second-Phase {beta}-Cell Secretion in the Offspring of Patients With Type 2 Diabetes: Studies With a Minimal Model to Assess {beta}-Cell Function Diabetes, February 1, 2003; 52(2): 470 - 480. [Abstract] [Full Text] [PDF]

				R. D'Alfonso, M. A. Marini, L. Frittitta, R. Sorge, S. Frontoni, O. Porzio, L. M. Mariani, D. Lauro, S. Gambardella, V. Trischitta, et al. Polymorphisms of the Insulin Receptor Subtrate-2 in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 317 - 322. [Abstract] [Full Text] [PDF]

				L. M. 't Hart, G. Nijpels, J. M. Dekker, J. A. Maassen, R. J. Heine, and T. W. van Haeften Variations in Insulin Secretion in Carriers of Gene Variants in IRS-1 and -2 Diabetes, March 1, 2002; 51(3): 884 - 887. [Abstract] [Full Text] [PDF]