Influence of aging on the alpha 1-receptor-mediated glycogenolysis in rat hepatocytes.
The involvement of the Ca(2+)-dependent and Ca(2+)-independent, insulin-sensitive pathway in the alpha 1-receptor-control of glycogenolysis was investigated in hepatocytes from young adult, mature adult, and senescent rats. Upon chelation of extracellular Ca2+, phenylephrine caused a similar increase in glucose output that was potently inhibited by insulin, indicating the presence of both pathways in each age group. From the age-related decreasing sensitivity of the Ca(2+)-dependent pathway toward verapamil and nifedipine, and toward insulin, we suggest that the contribution of Ca(2+)-fluxes in eliciting glycogenolysis through the Ca(2+)-dependent pathway decreases upon aging. Both pathways were inhibited by the protein kinase C (PKC) activator, 4 beta-phorbol 12-myristate 13-acetate (PMA); the inhibitory effect was decreased in hepatocytes from mature adult and senescent rats. In conclusion, our results favor the idea that a Ca(2+)-dependent and a Ca(2+)-independent, insulin-sensitive pathway remain involved throughout the life span. We provided the evidence for an impaired regulatory role of protein kinase C and calcium in hepatocytes from the older age groups.
Van Ermen
A
A
Heymans Institute of Pharmacology, Gent, Belgium.
Fraeyman
N
N
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007328:Insulin; D008112:Liver Glycogen; D018340:Receptors, Adrenergic, alpha-1; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium