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1Department of Pathobiology, Lerner Research Institute; 2Department of Gastroenterology and Hepatology, Cleveland Clinic; 3Department of Physiology, Case Western Reserve University, School of Medicine; 4Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio; 5Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota; 6Division of Pediatric Endocrinology, School of Medicine, University of California San Diego; and 7Division of Diabetes, Endocrinology and Metabolism, Veterans Affairs San Diego Health Care System, San Diego, California
Submitted 23 February 2007 ; accepted in final form 8 May 2007
Circulating adiponectin is reduced in disorders associated with insulin resistance. This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle. Impaired glucose-tolerant older (>60 yr) obese (BMI 3040 kg/m2) men (n = 7) and women (n = 14) were randomly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric (ExHypo,
500 kcal reduction, n = 11) or eucaloric diet (ExEu, n = 10). Insulin sensitivity was determined by the euglycemic (5.0 mM) hyperinsulinemic (40 mU·m2·min1) clamp. Adiponectin multimers [high (HMW), middle (MMW), and low molecular weight (LMW)] were measured by nondenaturing Western blot analysis. Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy samples. Greater weight loss occurred in ExHypo compared with ExEu subjects (8.0 ± 0.6 vs. 3.2 ± 0.6%, P < 0.0001). Insulin sensitivity improved postintervention in both groups (ExHypo: 2.5 ± 0.3 vs. 4.4 ± 0.5 mg·kg FFM1·min1, and ExEu: 2.9 ± 0.4 vs. 4.1 ± 0.4 mg·kg FFM1·min1, P < 0.0001). Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW (P < 0.03). The adiponectin SA ratio (HMW/total) was increased following both interventions (P < 0.05) and correlated with the percent change in insulin sensitivity (P < 0.03). Postintervention adiponectin receptor mRNA expression was also significantly increased (AdipoR1 P < 0.03, AdipoR2 P < 0.02). These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression.
glucose intolerance; diabetes; obesity; aging; gene expression
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