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, 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 [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;
2003-01-01

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.
2003
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., 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 [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; Fede...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/50470
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