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


METHODS
We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using (31)P/(1)H 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 x kg(-1) x 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 micromol x l(-1) x 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.
Szendroedi
Julia
J
First Medical Department, Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria.
Schmid
Albrecht Ingo
AI
Meyerspeer
Martin
M
Cervin
Camilla
C
Kacerovsky
Michaela
M
Smekal
Gerhard
G
Gräser-Lang
Sabine
S
Groop
Leif
L
Roden
Michael
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004734:Energy Metabolism; D005260:Female; D005949:Glucose Oxidase; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D017241:MELAS Syndrome / Q000503:physiopathology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D012016:Reference Values; D013147:Spirometry
D001786:Blood Glucose; D007328:Insulin; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D005949:Glucose Oxidase