Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1α and PPARβ/δ gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus

Autor: Marco Mensink, Patrick Schrauwen, Aaron P. Russell, Gert Schaart, Matthijs K. C. Hesselink, J. P. J. E. Sels
Přispěvatelé: Humane Biologie, Bewegingswetenschappen, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: NUTRIM - R1 - Metabolic Syndrome
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: International Journal of Obesity, 31(8), 1302-1310
International Journal of Obesity, 31(8), 1302-1310. Nature Publishing Group
International Journal of Obesity 31 (2007) 8
ISSN: 0307-0565
Popis: Objective:To examine whether rosiglitazone alters gene expression of some key genes involved in mitochondrial biogenesis and oxidative capacity in skeletal muscle of type 2 diabetic patients, and whether this is associated with alterations in skeletal muscle oxidative capacity and lipid content.Design:Skeletal muscle gene expression, mitochondrial protein content, oxidative capacity and lipid accumulation were measured in muscle biopsies obtained from diabetic patients, before and after 8 weeks of rosiglitazone treatment, and matched controls. Furthermore, whole-body insulin sensitivity and substrate utilization were assessed.Subjects:Ten obese type 2 diabetic patients and 10 obese normoglycemic controls matched for age and BMI.Methods:Gene expression and mitochondrial protein content of complexes I-V of the respiratory chain were measured by quantitative polymerase chain reaction and Western blotting, respectively. Histochemical staining was used to quantify lipid accumulation and complex II succinate dehydrogenase (SDH) activity. Insulin sensitivity and substrate utilization were measured during a hyperinsulinemic-euglycemic clamp with indirect calorimetry.Results:Skeletal-muscle mRNA of PGC-1alpha and PPARbeta/delta - but not of other genes involved in glucose, fat and oxidative metabolism - was significantly lower in diabetic patients (P
Databáze: OpenAIRE