It was reported that the common. -866G/A polymorphisin 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 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.

A Common Polymorphism in the Promoter of UCP2 Contributes to the Variation in Insulin Secretion in Glucose-Tolerant Subjects

DEL GUERRA, SILVIA;DEL PRATO, STEFANO;MARCHETTI, PIERO;
2003-01-01

Abstract

It was reported that the common. -866G/A polymorphisin 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 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, Ma; Frontoni, S; Dadamo, M; DEL GUERRA, Silvia; Lauro, D; DE NICOLAIS, P; Sbraccia, P; DEL PRATO, Stefano; Gambardella, S; Federici, M; Marchetti, Piero; Lauro, R.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/184631
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