HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db07-0141v1 56/8/2142    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Toledo, F. G.S. Articles by Kelley, D. E. Search for Related Content PubMed PubMed Citation Articles by Toledo, F. G.S. Articles by Kelley, D. E. Social Bookmarking                What's this?

Effects of Physical Activity and Weight Loss on Skeletal Muscle Mitochondria and Relationship With Glucose Control in Type 2 Diabetes

From the Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Address correspondence and reprint requests to Frederico G.S. Toledo, 807N Montefiore Hospital, 3459 Fifth Ave., Pittsburgh, PA 15213. E-mail: toledofs{at}upmc.edu

Abbreviations: mtDNA, mitochondrial DNA

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 VO_2max (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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. G.S. Toledo, E. V. Menshikova, K. Azuma, Z. Radikova, C. A. Kelley, V. B. Ritov, and D. E. Kelley Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content Diabetes, April 1, 2008; 57(4): 987 - 994. [Abstract] [Full Text] [PDF]

				M. Blatnik, N. Frizzell, S. R. Thorpe, and J. W. Baynes Inactivation of Glyceraldehyde-3-Phosphate Dehydrogenase by Fumarate in Diabetes: Formation of S-(2-Succinyl)Cysteine, a Novel Chemical Modification of Protein and Possible Biomarker of Mitochondrial Stress Diabetes, January 1, 2008; 57(1): 41 - 49. [Abstract] [Full Text] [PDF]