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

Abstract

Increase in fat mass (FM) and changes in body composition may account for the age-associated impairment in insulin action on muscle glycogen storage. We wish to examine whether preventing the increase in FM abolishes this defect seen with aging. We studied the novel aging model of F1 hybrids of BN/F344 NIA rats fed ad libitum (AL) at 2 (weighing 259 ± 17 g), 8 (459 ± 17 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 caloric intake by 45% (weighing 292 ± 5 g at 8 mo, 294 ± g at 20 mo). As designed, 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 rats. However, 8- and 20-mo-old AL-fed rats had three- to fourfold higher FM than both CR groups. Peripheral insulin action at physiological hyperinsulinemia was determined (by 3 mU ⋅ kg−1 ⋅ min−1insulin clamp). Prevention of fat accretion maintained glucose uptake (Rd; 29 ± 2, 29 ± 2, and 31 ± 4 mg ⋅ kg LBM−1 ⋅ min−1) and glycogen synthesis rates (GS, 12 ± 1, 12 ± 1, and 14 ± 2 mg ⋅ kg LBM−1 ⋅ min−1) at youthful levels (2 mo AL) in 8- and 20-mo-old CR rats, respectively. These levels were significantly increased ( P < 0.001) compared with AL rats with higher %FM (Rd, 22 ± 1 and 22 ± 2 and GS, 7 ± 1 and 8 ± 2 mg ⋅ kg LBM−1 ⋅ min−1in 8- and 20-mo-old rats, respectively). The increase in whole body GS in age-matched CR rats was accompanied by ∼40% increased accumulation of [3H]glucose into glycogen and a similar increase in insulin-induced muscle glycogen content. Furthermore, the activation of glycogen synthase increased, i.e., ∼50% decrease in the Michaelis constant, in both CR groups ( P < 0.01). We conclude that chronic CR designed to prevent an increase in storage of energy in fat maintained peripheral insulin action at youthful levels, and aging per se does not result in a defect on the pathway of glycogen storage in skeletal muscle.