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- Title
m.3243A>G mutation in mitochondrial DNA leads to decreased insulin sensitivity in skeletal muscle and to progressive beta-cell dysfunction.
- Authors
Lindroos MM; Majamaa K; Tura A; Mari A; Kalliokoski KK; Taittonen MT; Iozzo P; Nuutila P; Lindroos, Markus M; Majamaa, Kari; Tura, Andrea; Mari, Andrea; Kalliokoski, Kari K; Taittonen, Markku T; Iozzo, Patricia; Nuutila, Pirjo
- Abstract
<bold>Objective: </bold>To study insulin sensitivity and perfusion in skeletal muscle together with the beta-cell function in subjects with the m.3243A>G mutation in mitochondrial DNA, the most common cause of mitochondrial diabetes.<bold>Research Design and Methods: </bold>We measured skeletal muscle glucose uptake and perfusion using positron emission tomography and 2-[18F]fluoro-2-deoxyglucose and [15O]H2O during euglycemic hyperinsulinemia in 15 patients with m.3243A>G. These patients included five subjects with no diabetes as defined by the oral glucose tolerance test (OGTT) (group 1), three with GHb <6.1% and newly found diabetes by OGTT (group 2), and seven with a previously diagnosed diabetes (group 3). Control subjects consisted of 13 healthy individuals who were similar to the carriers of m.3243A>G with respect to age and physical activity. Beta-cell function was assessed using the OGTT and subsequent mathematical modeling.<bold>Results: </bold>Skeletal muscle glucose uptake was significantly lower in groups 1, 2, and 3 than in the control subjects. The glucose sensitivity of beta-cells in group 1 patients was similar to that of the control subjects, whereas in group 2 and 3 patients, the glucose sensitivity was significantly lower. The insulin secretion parameters correlated strongly with the proportion of m.3243A>G mutation in muscle.<bold>Conclusions: </bold>Our findings show that subjects with m.3243A>G are insulin resistant in skeletal muscle even when beta-cell function is not markedly impaired or glucose control compromised. We suggest that both the skeletal muscle insulin sensitivity and the beta-cell function are affected before the onset of the mitochondrial diabetes caused by the m.3243A>G mutation.
- Publication
Diabetes, 2009, Vol 58, Issue 3, p543
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db08-0981