Subjects With Early-Onset Type 2 Diabetes Show Defective Activation of the Skeletal Muscle PGC-1a/Mitofusin-2 Regulatory Pathway in Response to Physical Activity  

Oleh:

Hernandez-Alvarez, Maria Isabel ; Thabit, Hood ; Burns, Nicole ; Shah, Syed

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 33 no. 03 (Mar. 2010), page 645-651.
Topik: DIABETES; DIABETES MELLITUS; Type 2 Diabetes; Defective Activation; Skeletal Muscle PGC-1a/Mitofusin-2

Ketersediaan

Perpustakaan FK Nomor Panggil: D05.K.2010.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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 ? coactivator (PGC)-1a/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 a-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 a-subunit of ATP synthase in muscle from control subjects. However, Mfn2 was unchanged after chronic exercise in individuals with diabetes, whereas porin and a-subunit of ATP synthase were increased. Acute exercise caused a fourfold increase in PGC-1a expression in muscle from control subjects but not in subjects with diabetes. CONCLUSIONS : Our results demonstrate alterations in the regulatory pathway that controls PGC-1a 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-1a and Mfn2.

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