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Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins.

In English

Författare

Summary, in English

Genetic and environmental factors contribute to age-dependent susceptibility to type 2 diabetes. Recent studies have reported reduced expression of PPAR{gamma} coactivator 1{alpha} (PGC-1{alpha}) and PGC-1ß genes in skeletal muscle from type 2 diabetic patients, but it is not known whether this is an inherited or acquired defect. To address this question we studied expression of these genes in muscle biopsies obtained from young and elderly dizygotic and monozygotic twins without known diabetes before and after insulin stimulation and related the expression to a Gly482Ser variant in the PGC-1{alpha} gene. Insulin increased and aging reduced skeletal muscle PGC-1{alpha} and PGC-1ß mRNA levels. This age-dependent decrease in muscle gene expression was partially heritable and influenced by the PGC-1{alpha} Gly482Ser polymorphism. In addition, sex, birth weight, and aerobic capacity influenced expression of PGC-1{alpha} in a complex fashion. Whereas expression of PGC-1{alpha} in muscle was positively related to insulin-stimulated glucose uptake and oxidation, PGC-1ß expression was positively related to fat oxidation and nonoxidative glucose metabolism. We conclude that skeletal muscle PGC-1{alpha} and PGC-1ß expression are stimulated by insulin and reduced by aging. The data also suggest different regulatory functions for PGC-1{alpha} and PGC-1ß on glucose and fat oxidation in muscle cells. The finding that the age-dependent decrease in the expression of these key genes regulating oxidative phosphorylation is under genetic control could provide an explanation by which an environmental trigger (age) modifies genetic susceptibility to type 2 diabetes.

Avdelning/ar

Publiceringsår

2004

Språk

Engelska

Sidor

1518-1526

Publikation/Tidskrift/Serie

Journal of Clinical Investigation

Volym

114

Issue

10

Dokumenttyp

Artikel i tidskrift

Förlag

The American Society for Clinical Investigation

Ämne

  • Endocrinology and Diabetes
  • Nutrition and Dietetics

Status

Published

Forskningsgrupp

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Clinical Obesity

ISBN/ISSN/Övrigt

  • ISSN: 0021-9738