Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes

Frederico G.S. Toledo, Elizabeta V. Menshikova, Vladimir B. Ritov, Koichiro Azuma, Zofia Radikova, James DeLany, David E. Kelley

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203 Citations (Scopus)

Abstract

OBJECTIVE - Reduced mitochondrial capacity in skeletal muscle occurs in type 2 diabetic patients and in those at increased risk for this disorder, but the extent to which mitochondrial dysfunction in type 2 diabetic patients is remediable by physical activity and weight loss intervention is uncertain. We sought to address whether an intervention of daily moderate-intensity exercise combined with moderate weight loss can increase skeletal muscle mitochondrial content in type 2 diabetic patients and to address the relationship with amelioration of insulin resistance and hyperglycemia. RESEARCH DESIGN AND METHODS - Muscle biopsies were obtained before and after a 4-month intervention to assess mitochondrial morphology, mitochondrial DNA content, and mitochondrial enzyme activities. Glucose control, body composition, aerobic fitness, and insulin sensitivity were measured. RESULTS - In response to a weight loss of 7.1 ± 0.8% and a 12 ± 1.6% improvement in VO2max (P < 0.05), insulin sensitivity improved by 59 ± 21% (P < 0.05). There were significant increases in skeletal muscle mitochondrial density (by 67 ± 17%, P < 0.01), cardiolipin content (55 ± 17%, P < 0.01), and mitochondrial oxidation enzymes. Energy expenditure during physical activity correlated with the degree of improvement in insulin sensitivity (r = 0.84, P < 0.01), and, in turn, improvement in mitochondrial content was a strong correlate of intervention-induced improvement in A1C and fasting plasma glucose. CONCLUSIONS - Intensive short-term lifestyle modifications can restore mitochondrial content and functional capacity in skeletal muscle in type 2 diabetic patients. The improvement in the oxidative capacity of skeletal muscle may be a key component mediating salutary effects of lifestyle interventions on hyperglycemia and insulin resistance.

Original languageEnglish
Pages (from-to)2142-2147
Number of pages6
JournalDiabetes
Volume56
Issue number8
DOIs
Publication statusPublished - 2007 Aug 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Toledo, F. G. S., Menshikova, E. V., Ritov, V. B., Azuma, K., Radikova, Z., DeLany, J., & Kelley, D. E. (2007). Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes. Diabetes, 56(8), 2142-2147. https://doi.org/10.2337/db07-0141