Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
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- 1 October 2002
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 51 (10), 2944-2950
- https://doi.org/10.2337/diabetes.51.10.2944
Abstract
Skeletal muscle is strongly dependent on oxidative phosphorylation for energy production. Because the insulin resistance of skeletal muscle in type 2 diabetes and obesity entails dysregulation of the oxidation of both carbohydrate and lipid fuels, the current study was undertaken to examine the potential contribution of perturbation of mitochondrial function. Vastus lateralis muscle was obtained by percutaneous biopsy during fasting conditions from lean (n = 10) and obese (n = 10) nondiabetic volunteers and from volunteers with type 2 diabetes (n = 10). The activity of rotenone-sensitive NADH:O2 oxidoreductase, reflecting the overall activity of the respiratory chain, was measured in a mitochondrial fraction by a novel method based on providing access for NADH to intact mitochondria via alamethicin, a channel-forming antibiotic. Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively. Activity of rotenone-sensitive NADH:O2 oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity. NADH:O2 oxidoreductase activity was lowest in type 2 diabetic subjects and highest in the lean volunteers (lean 0.95 ± 0.17, obese 0.76 ± 0.30, type 2 diabetes 0.56 ± 0.14 units/mU creatine kinase; P < 0.005). Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 ± 0.74, obese 3.24 ± 0.82, type 2 diabetes 2.48 ± 0.47 units/mU creatine kinase; P < 0.005). As measured by electron microscopy, skeletal muscle mitochondria were smaller in type 2 diabetic and obese subjects than in muscle from lean volunteers (P < 0.01). We conclude that there is an impaired bioenergetic capacity of skeletal muscle mitochondria in type 2 diabetes, with some impairment also present in obesity.Keywords
This publication has 46 references indexed in Scilit:
- Ultra-high-resolution scanning electron microscopy of mitochondria and sarcoplasmic reticulum arrangement in human red, white, and intermediate muscle fibersThe Anatomical Record, 1997
- Increased prevalence of mitochondrial DNA deletions in skeletal muscle of older individuals with impaired glucose tolerance: possible marker of glycemic stressDiabetes, 1997
- Mitochondrial decay in agingBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- Mitochondrial DNA mutations in human degenerative diseases and agingBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus.JCI Insight, 1994
- Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by13C Nuclear Magnetic Resonance SpectroscopyThe New England Journal of Medicine, 1990
- Quantitative Ultrastructure of Mammalian Skeletal MusclePublished by Wiley ,1983
- Body weight, skeletal muscle morphology, and enzyme activities in relation to fasting serum insulin concentration and glucose tolerance in 48-year-old menDiabetes, 1981
- Enzyme activities in quadriceps femoris muscle of obese diabetic male patientsDiabetologia, 1977
- Metabolic changes in the quadriceps femoris muscle of obese peoplePflügers Archiv - European Journal of Physiology, 1975