Impaired mitochondrial function and insulin resistance of skeletal muscle in mitochondrial diabetes
J Szendroedi, AI Schmid, M Meyerspeer… - Diabetes …, 2009 - Am Diabetes Assoc
J Szendroedi, AI Schmid, M Meyerspeer, C Cervin, M Kacerovsky, G Smekal, S Gräser-Lang…
Diabetes care, 2009•Am Diabetes AssocOBJECTIVE 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 …
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 …
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 μmol · 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.
Am Diabetes Assoc