Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training

This study investigated alterations in glucagon receptor-mediated signal transduction in rat livers from 7- to 25-mo-old animals and examined the effects of exercise training on ameliorating these changes. Sixty-six young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats were divided into sedentary and trained (treadmill running) groups. Isolated hepatic membranes were combined with [125I-Tyr10]monoiodoglucagon and nine concentrations of glucagon to determine maximal binding capacity (Bmax) and dissociation constant (K d). No alterations were found in Bmax among groups; however, middle-aged trained animals had significantly higher glucagon affinity (lowerK d; 21.1 ± 1.8 nM) than did their untrained counterparts (50.2 ± 7.1 nM). Second messenger studies were performed by measuring adenylyl cyclase (AC) specific activity under basal conditions and with four pharmacological stimulations to assess changes in receptor-dependent, G protein-dependent, and AC catalyst-dependent cAMP production. A...