Diacylglycerols modulate phosphorylation of the insulin receptor from human mononuclear cells.
It has been found that 1,2- but not 1,3-diacylglycerols stimulated phosphorylation of the insulin receptor of cultured human monocyte-like (U-937) and lymphoblastoid (IM-9) cells both in the intact- and broken-cell systems. The stimulation of the receptor's beta-subunit phosphorylation was dose-dependent, with optimal effect at 100 micrograms/ml of diacylglycerol. The effects of insulin and 1,2-diacylglycerols on the phosphorylation of partially purified insulin receptors were additive. Phosphoamino acid analysis showed a major effect of diacylglycerols on phosphorylation of tyrosine residues. The diacylglycerols also stimulated tyrosine kinase activity of the partially purified U-937 and IM-9 insulin receptors 2.5-3.5-fold when measured by phosphorylation of an exogenous substrate, poly(Glu80Tyr20) in the absence of any added insulin, calcium or phospholipid. Since this diacylglycerol effect could not be reproduced under conditions optimal for protein kinase C activation and the purified protein kinase C did not stimulate phosphorylation of the beta-subunit of the insulin receptor in this system, it is unlikely that the diacylglycerol effect was mediated by protein kinase C. Since these exogenous 1,2-diacylglycerols at the same high concentration also inhibited 125I-insulin binding to the insulin receptor of the intact U-937 and IM-9 cells, diacylglycerols could modulate the function of the insulin receptor and insulin action in human mononuclear cells.
Department of Internal Medicine, Wayne State University School of Medicine, Detroit.
G
G
Grunberger
J
J
Levy
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000494:pharmacology; D011972:Receptor, Insulin / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004075:Diglycerides; D005989:Glycerides; D007328:Insulin; D011972:Receptor, Insulin; D011493:Protein Kinase C