Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

被引:60
作者
Szendroedi, Julia [1 ,2 ,3 ]
Schmid, Albrecht Ingo [1 ,2 ,4 ]
Meyerspeer, Martin [4 ]
Cervin, Camilla [5 ]
Kacerovsky, Michaela [1 ,2 ]
Smekal, Gerhard [6 ]
Graeser-Lang, Sabine [7 ]
Groop, Leif [5 ]
Roden, Michael [1 ,2 ,3 ]
机构
[1] Hanusch Hosp, Dept Med 1, Vienna, Austria
[2] Hanusch Hosp, Karl Landsteiner Inst Endocrinol & Metab, Vienna, Austria
[3] Univ Dusseldorf, Dept Med Metab Dis, Leibniz Ctr, German Diabet Ctr,Inst Clin Diabetol, Dusseldorf, Germany
[4] Med Univ Vienna, MR Ctr Excellence, Vienna, Austria
[5] Lund Univ, Dept Clin Sci, Lund, Sweden
[6] Univ Vienna, Inst Sports Sci, Dept Sport Physiol, Vienna, Austria
[7] Hanusch Hosp, Neurol Outpatient Serv, Vienna, Austria
关键词
TRNA(LEU(UUR)) GENE MUTATION; QUANTIFICATION; SENSITIVITY; DYSFUNCTION; MECHANISMS; DEAFNESS; HUMANS;
D O I
10.2337/dc08-2078
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective beta-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS - We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using P-31/H-1 magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS(myopathy,encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects. RESULTS - The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 +/- 0.5 mg . kg(-1) . min(-1)) and suppression of EGP (69 vs. 94 +/- 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 +/- 1.0 and 12.8 +/- 1.3 mu mol . l(-1) . min(-1)) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects. CONCLUSIONS - Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome.
引用
收藏
页码:677 / 679
页数:3
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