Genetic Factors and Insulin Secretion
Gene Variants in the IGF Genes
- Leen M. ’t Hart1,
- Andreas Fritsche2,
- Ingrid Rietveld3,
- Jacqueline M. Dekker4,
- Giel Nijpels4,
- Fausto Machicao2,
- Michael Stumvoll2,
- Cornelia M. van Duijn3,
- Hans U. Häring2,
- Robert J. Heine4,
- J. Antonie Maassen14 and
- Timon W. van Haeften5
- 1Deparment of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands
- 2Department of Internal Medicine, Universitätsklinikum Tübingen, Tübingen, Germany
- 3Department of Epidemiology and Biostatistics, Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam, the Netherlands
- 4Institute for Research in Extramural Medicine, Free University Medical Center, Amsterdam, the Netherlands
- 5Department of Internal Medicine, University Medical Center, Utrecht, the Netherlands
- Address correspondence and reprint requests to J. Antonie Maassen, LUMC, Department of Molecular Cell Biology, Wassenaarseweg 72, 2333 AL Leiden, Netherlands. E-mail: j.a.maassen{at}lumc.nl
Abstract
IGFs are important regulators of pancreatic β-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes-related parameters were not significantly different for both the IGF-I and IGF-II gene variant. We conclude that gene variants in the IGF-I and IGF-II genes are not associated with detectable variations in glucose-stimulated insulin secretion in these three independent populations. Further studies are needed to examine the exact contributions of the IGF-I CA repeat alleles to variations in ISI and DI.
- DI, disposition index
- IGT, impaired glucose tolerance
- ISI, insulin sensitivity index
- NGT, normal glucose tolerance
- OGTT, oral glucose tolerance test
- RFLP, restriction fragment length polymorphism
Footnotes
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This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Les Laboratoires Servier.
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- Accepted June 11, 2003.
- Received March 12, 2003.
- DIABETES
