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Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training
- Source :
- The American Journal of Physiology. Sept, 2001, Vol. 281 Issue 3, E516
- Publication Year :
- 2001
-
Abstract
- 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 [[sup.125]I-[Tyr.sup.10]]monoiodoglucagon and nine concentrations of glucagon to determine maximal binding capacity ([B.sub.max]) and dissociation constant ([K.sub.d]). No alterations were found in [B.sub.max] among groups; however, middle-aged trained animals had significantly higher glucagon affinity (lower [K.sub.d]; 21.1 [+ or -] 1.8 nM) than did their untrained counterparts (50.2 [+ or -] 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. Age-related declines were observed in the old animals under all five conditions. Training resulted in increased cAMP production in the old animals when AC was directly stimulated by forskolin. Stimulatory G protein ([G.sub.S]) content was reduced with age in the sedentary group; however, training offset this decline. We conclude that age-related declines in glucagon signaling capacity and responsiveness may be attributed, in part, to declines in intrinsic AC activity and changes in G protein [inhibitory G protein ([G.sub.i])/[G.sub.S]] ratios. These age-related changes occur in the absence of alterations in glucagon receptor content and appear to involve both G protein- and AC-related changes. Endurance training was able to significantly offset these declines through restoration of the [G.sub.i]/[G.sub.S] ratio and AC activity. adenylyl cyclase; hepatic membranes; GTP-binding proteins; gluconeogenesis; aging; glucose homeostasis
- Subjects :
- Cellular signal transduction -- Physiological aspects
Glucagon -- Physiological aspects
Aging -- Physiological aspects
Rats as laboratory animals -- Research
Liver -- Glycogenic function
Exercise -- Physiological aspects
Adenylate cyclase -- Physiological aspects
G proteins -- Physiological aspects
Biological sciences
Subjects
Details
- ISSN :
- 00029513
- Volume :
- 281
- Issue :
- 3
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.78679423