title: Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats.
abstract: Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ∼24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ∼65% of ad libitum, AL, intake beginning at ∼22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulin-stimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr(309) and Ser(474) along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr(642) and Ser(588), filamin C on Ser(2213) and proline-rich Akt substrate of 40 kDa on Thr(246), but not TBC1D1 on Thr(596); and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals.
authors.affiliation: 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.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan;
authors.forename: Edward B
authors.initials: EB
authors.lastname: Arias
authors.affiliation: 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.forename: Gregory D
authors.initials: GD
authors.lastname: Cartee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D003433:Crosses, Genetic; D003847:Deoxyglucose / Q000378:metabolism*; D004789:Enzyme Activation; D064448:Filamins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C516104:Akt1s1 protein, rat; D064448:Filamins; D020690:GTPase-Activating Proteins; D007328:Insulin; D047428:Protein Kinase Inhibitors; C533101:TBC1D4 protein, rat; D003847:Deoxyglucose; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt
keywords: aging; glucose transport; insulin resistance; insulin signaling