Adrenergic stimulated skeletal muscle glycogenolysis in perfused hindlimbs of young and old male Fischer 344 rats.

Abstract

Epinephrine (Epi)- and forskolin (FSK)-stimulated glycogenolysis of skeletal muscle was evaluated in perfused hindlimb isolated from male Fischer 344 (F344) rats, ages 6, 12, and 26 mo. Muscle glycogen stores were reduced by sciatic nerve stimulation and replenished by infusing 10 mM glucose, 500 microU insulin, and 5 microCi [14C]glucose via a left carotid artery cannula. Then the hindlimb was perfused with a modified Krebs-Henseleit buffer (pH 7.4). At minute 20 of the perfusion, Epi [0.0 (perfusate), 0.25, 0.50, or 0.75 microM] or 40 microM FSK were infused for 10 min. Radioactivity (14C) in the effluent perfusate was collected every 60 s during a 20-min preinfusion, a 10-min Epi infusion, and a 20-min postinfusion period and was used to determine the rate of muscle glycogen utilization. Total 14C release increased with Epi and 40 microM FSK. However, the pattern of release did not differ significantly with age. In general, the fraction of the perfusate released as 14CO2 increased in the presence of FSK and Epi but did not significantly differ with age. [14C]lactate released in response to Epi increased in the 6-mo-old group, remained unchanged in the 12-mo-old group, and decreased in the 26-mo-old group compared with 0.0 Epi (perfusate) values. It appears that stimulation of skeletal muscle glycogenolysis via adrenergic receptor or postreceptor/adenosine 3',5'-cyclic monophosphate-mediated mechanisms is unaffected by age. However, the utilization of carbohydrate by isolated hindlimb muscle is altered in the aging rat, resulting in a more oxidative metabolism.