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Diabetologia. 2007 Aug;50(8):1615-20. Epub 2007 Jun 20.

Impact of the peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1beta expression and fibre type composition in human skeletal muscle.

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  • 1Department of Clinical Sciences/Diabetes and Endocrinology, Lund University, CRC, University Hospital MAS, 205 02 Malmo, Sweden. charlotte.ling@med.lu.se

Abstract

AIMS/HYPOTHESIS:

Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta, also known as PPARGC1B) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1beta expression, in vivo metabolism and markers for muscle fibre type composition.

MATERIALS AND METHODS:

The PGC-1beta Ala203Pro polymorphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1beta expression, in vivo metabolism and markers for fibre type composition.

RESULTS:

Insulin-stimulated non-oxidative glucose metabolism (NOGM; p = 0.025) and glycolytic flux rate (GF; p = 0.026) were reduced in young Ala/Ala carriers compared with carriers of a 203Pro allele. In addition, a regression analysis, correcting for covariates, showed that the PGC-1beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p < or = 0.001), there was no significant age-related decline in PGC-1beta expression in carriers of the 203Pro allele (p > or = 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1beta expression. Finally, PGC-1beta expression correlated positively with markers for oxidative fibres in human muscle.

CONCLUSIONS/INTERPRETATION:

This study suggests that young carriers of a PGC-1beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1beta expression in muscle.

[PubMed - indexed for MEDLINE]
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