Effect of diabetes on hormone-stimulated and basal hepatocyte calcium metabolism.
The effects of diabetes on basal calcium metabolism and the response to endocrine stimulation were studied in hepatocytes from acute and long term diabetic rats. Hepatocyte calcium sequestration and turnover were increased in both acute and chronic diabetes. Cytosolic free calcium (Cai2+) was significantly increased in the chronic diabetics, but the rise in Cai2+ evoked by epinephrine, angiotensin, vasopressin, and glucagon was depressed. The blunted stimulation of phosphorylase-alpha activity in the diabetics was influenced by a 50-60% decrease in total cell activity of glycogen phosphorylase and the decreased rise in cytosolic free calcium. Insulin replacement corrected both basal and stimulated changes in the acute diabetes model. Depressed [3H]inositol trisphosphate formation in response to epinephrine or vasopressin and increased intracellular organelle calcium buffering were observed in hepatocytes from diabetic animals; both may effect the diminished rise in Cai2+. Several possible causes for the depressed rise in Cai2+ after stimulation in chronic diabetic animals were eliminated: 1) the number and affinity of alpha 1-adrenergic receptors for epinephrine were normal; 2) the initial rise in calcium influx evoked by epinephrine or vasopressin was not depressed; and 3) the ability of inositol trisphosphate to release calcium from intracellular organelles was not changed. The results suggest that the diabetic changes in calcium-mediated endocrine regulation of hepatic carbohydrate metabolism contribute to the general pathology of the disease.
Studer
R K
RK
Department of Physiology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Ganas
L
L
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values
D011942:Receptors, Adrenergic, alpha; D001127:Arginine Vasopressin; D015544:Inositol 1,4,5-Trisphosphate; D005934:Glucagon; D006005:Phosphorylases; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine