Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1{alpha}/Mitofusin-2 regulatory pathway in response to physical activity.
Diabetes Care
; 33(3): 645-51, 2010 Mar.
Article
em En
| MEDLINE
| ID: mdl-20032281
ABSTRACT
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 Vo(2max) 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)-1alpha/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-1alpha expression in muscle from control subjects but not in subjects with diabetes. CONCLUSIONS Our results demonstrate alterations in the regulatory pathway that controls PGC-1alpha 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-1alpha and Mfn2.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Músculo Esquelético
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Proteínas Mitocondriais
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Diabetes Mellitus Tipo 2
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Proteínas de Choque Térmico
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Proteínas de Membrana
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Atividade Motora
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Espanha