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- Title
Genetic factors and insulin secretion: gene variants in the IGF genes.
- Authors
't Hart, Leen M; Fritsche, Andreas; Rietveld, Ingrid; Dekker, Jacqueline M; Nijpels, Giel; Machicao, Fausto; Stumvoll, Michael; van Duijn, Cornelia M; Häring, Hans U; Heine, Robert J; Maassen, J Antonie; van Haeften, Timon W
- Abstract
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.
- Subjects
GERMANY; NETHERLANDS; ALLELES; BLOOD sugar; COMPARATIVE studies; GENETICS; INSULIN; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; RESEARCH; RESEARCH evaluation; SOMATOMEDIN; EVALUATION research; GLUCOSE clamp technique
- Publication
Diabetes, 2004, Vol 53, pS26
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.2007.s26