Aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats

Increase in fat mass (FM) and changes in body composition may account for t he age-associated impairment in insulin action on muscle glycogen storage. We wish to examine whether preventing the increase in FM abolishes this def ect seen with aging. We studied the novel aging model of Fl hybrids of BN/F 344 NIA rats fed ad libitum (AL) at 2 (weighing 259 +/- 17 g), 8 (459 +/- 1 7 g), and 20 (492 +/- 10 g) mo old. To prevent the age-dependent growth in FM, rats were caloric restricted (CR) at 2 mo by decreasing their daily cal oric intake by 45% (weighing 292 +/- 5 g at 8 mo, 294 +/- g at 20 mo). As d esigned, the lean body mass (LBM) and %FM remained unchanged through aging (8 and 20 mo old) in the CR rats and was similar to that of 2-mo-old AL rat s. However, 8- and 20-mo-old AL-fed rats had three- to fourfold higher FM t han both CR groups. Peripheral insulin action at physiological hyperinsulin emia was determined (by 3 mU . kg(-1) . min(-1) insulin clamp). Prevention of fat accretion maintained glucose uptake (R-d; 29 +/- 2, 29 +/- 2, and 31 +/- 4 mg . kg LBM-1 . min(-1)) and glycogen synthesis rates (CTS, 12 +/- 1 , 12 +/- 1, and 14 +/- 2 mg . kg . LBM-1 . min(-1)) at youthful levels (2 m o AL) in 8- and 20-mo-old CR rats, respectively. These levels were signific antly increased (P < 0.001) compared with AL rats with higher %FM (R-d, 22 +/- 1 and 22 +/- 2 and GS, 7 +/- 1 and 8 +/- 2 mg . kg LBM-1 . min(-1) in 8 - and 20-mo-old rats, respectively). The increase in whole body GS in age-m atched CR rats was accompanied by similar to 40% increased accumulation of [H-3]glucose into glycogen and a similar increase in insulin-induced muscle glycogen content. Furthermore, the activation of glycogen synthase increas ed, i.e., similar to 50% decrease in the Michaelis constant, in both CR gro ups (P < 0.01). We conclude that chronic CR designed to prevent an increase in storage of energy in fat maintained peripheral insulin action at youthf ul levels, and aging per se does not result in a defect on the pathway of g lycogen storage in skeletal muscle.