Impaired mitochondrial function and insulin resistance of skeletal muscle in mitochondrial diabetes

Abstract

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 β-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 31P/1H 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 (xmol · 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. © 2009 by the American Diabetes Association.