Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes.
We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance (P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes in humans with obesity.
Mogensen
Martin
M
Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
Sahlin
Kent
K
Fernström
Maria
M
Glintborg
Dorte
D
Vind
Birgitte F
BF
Beck-Nielsen
Henning
H
Højlund
Kurt
K
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004579:Electron Transport; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D012016:Reference Values
D001786:Blood Glucose; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase