title: Mechanisms for independent and combined effects of calorie restriction and acute exercise on insulin-stimulated glucose uptake by skeletal muscle of old rats.
abstract: Either calorie restriction [CR; consuming 60-65% of ad libitum (AL) intake] or acute exercise can independently improve insulin sensitivity in old age, but their combined effects on muscle insulin signaling and glucose uptake have previously been unknown. Accordingly, we assessed the independent and combined effects of CR (beginning at 14 wk old) and acute exercise (3-4 h postexercise) on insulin signaling and glucose uptake in insulin-stimulated epitrochlearis muscles from 30-mo-old rats. Either CR alone or exercise alone vs. AL sedentary controls induced greater insulin-stimulated glucose uptake. Combined CR and exercise vs. either treatment alone caused an additional increase in insulin-stimulated glucose uptake. Either CR or exercise alone vs. AL sedentary controls increased Akt Ser(473) and Akt Thr(308) phosphorylation. Combined CR and exercise further elevated Akt phosphorylation on both sites. CR alone, but not exercise alone, vs. AL sedentary controls significantly increased Akt substrate of 160 kDa (AS160) Ser(588) and Thr(642) phosphorylation. Combined CR and exercise did not further enhance AS160 phosphorylation. Exercise alone, but not CR alone, modestly increased GLUT4 abundance. Combined CR and exercise did not further elevate GLUT4 content. These results suggest that CR or acute exercise independently increases insulin-stimulated glucose uptake via overlapping (greater Akt phosphorylation) and distinct (greater AS160 phosphorylation for CR, greater GLUT4 for exercise) mechanisms. Our working hypothesis is that greater insulin-stimulated glucose uptake in the combined CR and exercise group vs. CR or exercise alone relies on greater Akt activation, leading to greater phosphorylation of one or more Akt substrates other than AS160.
authors: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan; School of Health Sciences, Central Michigan University, Mount Pleasant, Michigan;
authors: Naveen
authors: N
authors: Sharma
authors: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan; College of Physical Education and Health, East China Normal University, Shanghai, China;
authors: Haiyan
authors: H
authors: Wang
authors: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan;
authors: Edward B
authors: EB
authors: Arias
authors: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan;
authors: Carlos M
authors: CM
authors: Castorena
authors: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; and Institute of Gerontology, University of Michigan, Ann Arbor, Michigan gcartee@umich.edu.
authors: Gregory D
authors: GD
authors: Cartee
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D015398:Signal Transduction
chemical_list: D007328:Insulin; D003847:Deoxyglucose; D005947:Glucose
keywords: aging; glucose transport; glucose transporter; insulin resistance; insulin signaling; physical activity