Back to Search
Start Over
m.3243A>G Mutation in Mitochondrial DNA Leads to Decreased Insulin Sensitivity in Skeletal Muscle and to Progressive γ-Cell Dysfunction.
- Source :
-
Diabetes . March2009, Vol. 58 Issue 3, p543-549. 7p. 2 Charts, 5 Graphs. - Publication Year :
- 2009
-
Abstract
- OBJECTIVE--To study insulin sensitivity and perfusion in skeletal muscle together with the β-cell function in subjects with the m.3243A>G mutation in mitochondrial DNA, the most common cause of mitochondrial diabetes. RESEARCH DESIGN AND METHODS--We measured skeletal muscle glucose uptake and perfusion using positron emission tomography and 2-[[sup 18]F]fluoro-2-deoxyglucose and [[sup 15]O]H[sub 2]O 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. β-Cell function was assessed using the OGTT and subsequent mathematical modeling. RESULTS--Skeletal muscle glucose uptake was significantly lower in groups 1, 2, and 3 than in the control subjects. The glucose sensitivity of β-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. CONCLUSIONS---Our findings show that subjects with m.3243A >G are insulin resistant in skeletal muscle even when β-cell function is not markedly impaired or glucose control compromised. We suggest that both the skeletal muscle insulin sensitivity and the β-cell function are affected before the onset of the mitochondrial diabetes caused by the m.3243A>G mutation. Diabetes 58:543-549, 2009 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 58
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 37248490
- Full Text :
- https://doi.org/10.2337/db08-0981