Genetic factors and insulin secretion: gene variants in the IGF genes
IGFs are important regulators of pancreatic beta-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.
|Keywords||*Variation (Genetics), 0 (Blood Glucose), 11061-68-0 (Insulin), 67763-96-6 (Insulin-Like Growth Factor I), 67763-97-7 (Insulin-Like Growth Factor II), Adult, Alleles, Blood Glucose/metabolism, Cohort Studies, Diabetes and related disorders, Female, Germany, Glucose Clamp Technique, Human, Insulin-Like Growth Factor I/*genetics, Insulin-Like Growth Factor II/*genetics, Insulin/blood/*secretion, Male, Middle Aged, Netherlands, Reproducibility of Results, Support, Non-U.S. Gov't|
't Hart, L.M., Fritsche, A., Rietveld, I., Dekker, J.M., Nijpels, M.G.A.A.M., Machicao, F., … van Haeften, T.W.. (2004). Genetic factors and insulin secretion: gene variants in the IGF genes. Diabetes, 53, 26–30. Retrieved from http://hdl.handle.net/1765/5941