Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 302, Issue 1, Pages E145-E152Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00618.2010
Keywords
skeletal muscle; insulin action; aerobic exercise training; weight loss; aging
Categories
Funding
- Baltimore Veterans Affairs Medical Research Service
- Veterans Affairs Research Career Scientist Award
- Department of Veterans Affairs and Veterans Affairs Medical Center GRECC
- National Institute on Aging [RO1-AG-19310, R01-AG-20116]
- Claude D. Pepper Older Americans Independence Center [P30-AG-028747]
- National Institute of Diabetes and Digestive and Kidney Diseases Mid-Atlantic Nutrition Obesity Research Center [NIH P30-DK-072488]
- General Clinical Research Center of the University of Maryland, Baltimore, Maryland [MO1-RR-016500]
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Ryan AS, Ortmeyer HK, Sorkin JD. Exercise with calorie restriction improves insulin sensitivity and glycogen synthase activity in obese postmenopausal women with impaired glucose tolerance. Am J Physiol Endocrinol Metab 302: E145-E152, 2012. First published October 18, 2011; doi:10.1152/ajpendo.00618.2010.-Our objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in normal (NGT) vs. impaired glucose-tolerant (IGT) obese postmenopausal women and to determine whether an increase in insulin activation of GS is associated with an improvement in insulin sensitivity (M) following calorie restriction (CR) and/or aerobic exercise plus calorie restriction (AEX + CR) in women with NGT and IGT. We did a longitudinal, clinical intervention study of CR compared with AEX + CR. Overweight and obese women, 49-76 yr old, completed 6 mo of CR (n = 46) or AEX + CR (n = 50) with (V) over dotO(2) (max), body composition, and glucose tolerance testing. Hyperinsulinemic euglycemic (80 mU.m(-2).min(-1)) clamps (n = 73) and skeletal muscle biopsies (before and during clamp) (n = 58) were performed before and after the interventions (n = 50). After 120 min of hyperinsulinemia during the clamp, GS fractional activity and insulin's effect to increase GS fractional activity (insulin = basal) were significantly lower in IGT vs. NGT (P < 0.01) at baseline. GS total activity increased during the clamp in NGT (P < 0.05), but not IGT, at baseline. CR and AEX + CR resulted in a significant 8% weight loss with reductions in total fat mass, visceral fat, subcutaneous fat, and intramuscular fat. Overall, M increased (P < 0.01), and the change in M (postintervention = preintervention) was associated with the change in insulin-stimulated GS fractional activity (partial r = 0.44, P < 0.005). In IGT, the change (postintervention = preintervention) in insulin-stimulated GS total activity was greater following AEX + CR than CR alone (P < 0.05). In IGT, insulin-stimulated GS-independent (P < 0.005) and fractional activity (P = 0.06) increased following AEX + CR. We conclude that the greatest benefits at the whole body and cellular level (insulin activation of GS) in older women at highest risk for diabetes are derived from a lifestyle intervention that includes exercise and diet.
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