It was reported that the common -866G/A polymorphism in the promoter of the human uncoupling protein-2 (UCP2) gene, which enhances its trascriptional activity, is associated with increased mRNA levels in human adipocytes and reduced risk of obesity. Studies in knockout mice and beta-cells indicate that UCP2 may play a role in beta-cell function. In this study, we addressed the question of whether the common -866G/A polymorphism in UCP2 gene contributes to the variation of insulin secretion in humans by genotyping 301 nondiabetic subjects who underwent an oral glucose tolerance test. Glucose-stimulated insulin secretion estimated by several indexes of beta-cell function was significantly lower in carriers of the -866A/A genotype compared with -866A/G or -866G/G according to the dosage of the A allele (P = 0.002-0.05). To investigate directly whether the UCP2 -866G/A polymorphism affects human islet function, pancreatic islets isolated from two -866G/G homozygous, seven -866G/A heterozygous, and one -866A/A homozygous nondiabetic donors were studied. Islets from -866A/A homozygous had lower insulin secretion in response to glucose stimulation as compared with -866G/G and -866G/A carriers. These results indicate that the common -866G/A polymorphism in the UCP2 gene may contribute to the biological variation of insulin secretion in humans.
Sesti, G., Cardellini, M., Marini, M.A., Frontoni, S., D'Adamo, M., Del Guerra, S., et al. (2003). A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. DIABETES, 52(5), 1280-1283.
|Tipologia:||Articolo su rivista|
|Citazione:||Sesti, G., Cardellini, M., Marini, M.A., Frontoni, S., D'Adamo, M., Del Guerra, S., et al. (2003). A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. DIABETES, 52(5), 1280-1283.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||mag-2003|
|Titolo:||A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects|
|Autori:||Sesti, G; Cardellini, M; Marini, MA; Frontoni, S; D'Adamo, M; Del Guerra, S; Lauro, D; De Nicolais, P; Sbraccia, P; Del Prato, S; Gambardella, S; Federici, M; Marchetti, P; Lauro, R|
|Appare nelle tipologie:||01 - Articolo su rivista|