Influence of aging on the beta- and glucagon-receptor-mediated glycogenolysis in rat hepatocytes.
The influence of aging on beta-receptor and glucagon-receptor control of glycogenolysis was investigated in rat hepatocytes. The beta-receptor-induced glucose output was detectable only in senescent rats, was partly dependent on extracellular Ca2+, and was inhibited by 4 beta-phorbol 12-myristate 13-acetate (PMA), insulin, and the Ca(2+)-antagonists, verapamil and nifedipine. Chelation of extracellular Ca2+ potentiated the effect of nifedipine only. In contrast, glucagon-stimulated glycogenolysis, similar in mature and senescent rats, was independent on extracellular Ca2+ and was unaffected by PMA. Verapamil, in senescent rats only, and nifedipine, in mature and senescent rats, inhibited glucagon-stimulated glucose output only in the presence of Ca2+. Insulin inhibited glucagon-induced glucose output, irrespective of the age of the rat and the presence of Ca2+. We conclude that the beta-receptor component in the adrenergic regulation of glycogenolysis in senescent rats consists of a major Ca(2+)-independent and a minor Ca(2+)-dependent part, displaying different sensitivity towards protein kinase C (PKC), Ca(2+)-antagonists, and insulin. Aging does not change the capacity of glucagon to induce a full glycogenolytic response in the absence of extracellular Ca2+; Ca(2+)-influx, however, seems to be involved when extracellular Ca2+ is present, and this sensitivity is increased on aging.
Fraeyman
N
N
Heymans Institute of Pharmacology, University of Gent, Belgium.
van Ermen
A
A
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018027:Receptors, Glucagon / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D008112:Liver Glycogen; D011943:Receptors, Adrenergic, beta; D018027:Receptors, Glucagon; D004533:Egtazic Acid; D014700:Verapamil; D011493:Protein Kinase C; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium