Insulin increases the synthesis of phospholipid and diacylglycerol and protein kinase C activity in rat hepatocytes.
The effects of insulin on phospholipid metabolism and generation of diacylglycerol (DAG) and on activation of protein kinase C in rat hepatocytes were compared to those of vasopressin and angiotension II. Insulin provoked increases in [3H]glycerol labeling of phosphatidic acid (PA), diacylglycerol (DAG), and other glycerolipids within 30 s of stimulation. Similar increases were also noted for vasopressin and angiotensin II. Corresponding rapid increases in DAG mass also occurred with all three hormones. As increases in [3H]DAG (and DAG mass) occurred within 30-60 s of the simultaneous addition of [3H]glycerol and hormone, it appeared that DAG was increased, at least partly, through the de novo synthesis of PA. That de novo synthesis of PA was increased is supported by the fact that [3H]glycerol labeling of total glycerolipids was increased by all three agents. Increases in [3H]glycerol labeling of lipids by insulin were not due to increased labeling of glycerol 3-phosphate, and were therefore probably due to activation of glycerol-3-phosphate acyltransferase. Unlike vasopressin, insulin did not increase the hydrolysis of inositol phospholipids. Insulin- and vasopressin-induced increases in DAG were accompanied by increases in cytosolic and membrane-associated protein kinase C activity. These findings suggest that insulin-induced increases in DAG may lead to increases in protein kinase C activity, and may explain some of the insulin-like effects of phorbol esters and vasopressin on hepatocyte metabolism.
Cooper
D R
DR
James A. Haley Veterans Hospital, Tampa, Florida 33612.
Hernandez
H
H
Kuo
J Y
JY
Farese
R V
RV
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004075:Diglycerides / Q000096:biosynthesis*; D004533:Egtazic Acid / Q000494:pharmacology; D005989:Glycerides / Q000096:biosynthesis*; D005990:Glycerol / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D007328:Insulin; D010743:Phospholipids; D014667:Vasopressins; D000804:Angiotensin II; D007294:Inositol; D004533:Egtazic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D005990:Glycerol; D002118:Calcium