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., C.M. (2003). A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. DIABETES [10.2337/diabetes.52.5.1280].

A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects

CARDELLINI, MARINA;MARINI, MARIA ADELAIDE;FRONTONI, SIMONA;D'Adamo M.;LAURO, DAVIDE;SBRACCIA, PAOLO;FEDERICI, MASSIMO;
2003

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/13 - Endocrinologia
English
insulin; messenger RNA; uncoupling protein 2; adipocyte; adult; aged; article; female; gene dosage; genetic polymorphism; genetic transcription; genotype; glucose tolerance; heterozygosity; homozygosity; human; human experiment; human tissue; insulin release; knockout mouse; male; normal human; obesity; oral glucose tolerance test; pancreas function; pancreas islet beta cell; priority journal; promoter region; risk factor; Adult; Blood Glucose; Female; Gene Expression Regulation; Genotype; Glucose Tolerance Test; Hemoglobin A, Glycosylated; Humans; Insulin; Ion Channels; Lipids; Male; Membrane Transport Proteins; Middle Aged; Mitochondrial Proteins; Polymorphism, Single Nucleotide; Promoter Regions (Genetics); Proteins; Transcription, Genetic
Sesti G., C.M. (2003). A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. DIABETES [10.2337/diabetes.52.5.1280].
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
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/50470
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