期刊
DIABETES CARE
卷 33, 期 3, 页码 645-651出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc09-1305
关键词
-
资金
- European Foundation for the Study of Diabetes/Novo Nordisk
- EU Commission [LHSM-CT-2003-503041]
- Ministerio de Educacion y Cultura, Spain [SAF 2005-00445, SAF 2008-03803]
- Generalitat de Catalunya [2005SGR00947]
- Consejo Nacional de Ciencia y Tecnologia, Mexico
- University of Barcelona
OBJECTIVE - Type 2 diabetes is associated with insulin resistance and skeletal muscle mitochondrial dysfunction. We have found that subjects with early-onset type 2 diabetes show incapacity to increase VO2max in response to chronic exercise. This suggests a defect in muscle mitochondrial response to exercise. Here, we have explored the nature of the mechanisms involved. RESEARCH DESIGN AND METHODS - Muscle biopsies were collected from young type 2 diabetic subjects and obese control subjects before and after acute or chronic exercise protocols, and the expression of genes and/or proteins relevant to mitochondrial function was measured. In particular, the regulatory pathway peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 alpha/mitofusin-2 (Mfn2) was analyzed. RESULTS - At baseline, subjects with diabetes showed reduced expression (by 26%) of the mitochondrial fusion protein Mfn2 and a 39% reduction of the alpha-subunit of ATP synthase. Porin expression was unchanged, consistent with normal mitochondrial mass. Chronic exercise led to a 2.8-fold increase in Mfn2, as well as increases in porin, and the alpha-subunit of ATP synthase in muscle from control subjects. However, Mfn2 was unchanged after chronic exercise in individuals with diabetes, whereas porin and alpha-subunit of ATP synthase were increased. Acute exercise caused a fourfold increase in PGC-1 alpha expression in muscle from control subjects but not in subjects with diabetes. CONCLUSIONS - Our results demonstrate alterations in the regulator pathway that controls PGC-1 alpha expression and induction of Mfn2 in muscle from patients with early-onset type 2 diabetes. Patients with early-onset type 2 diabetes display abnormalities in the exercise-dependent pathway that regulates the expression of PGC-1 alpha and Mfn2.
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