Insulin inhibits the phosphorylation of alpha-Gi-2 in intact hepatocytes.
Challenge of intact hepatocytes with insulin reduced the level of phosphorylated alpha-Gi-2 found under basal (resting) conditions. At maximally effective concentrations of insulin the steady-state labelling of alpha-Gi-2 was reduced by approximately 21%. Insulin achieved this in a time- and dose-dependent fashion, exhibiting an IC50 value of 109 +/- 22 pM. The increased labelling of alpha-Gi-2 seen after challenge of cells with phorbol 12-myristate 13-acetate was also attenuated by insulin. Treatment of hepatocytes with the protein phosphatase inhibitor okadaic acid increased the labelling of alpha-Gi-2 in a fashion which was insensitive to the action of insulin. It is suggested that insulin may reduce the level of phosphorylation of alpha-Gi-2 by stimulating intracellular protein phosphatase activity and that this action may offer a molecular explanation for the ability of insulin to inhibit adenylate cyclase activity in hepatocytes by increasing the level of non-phosphorylated alpha-Gi-2.
Morris
N J
NJ
Department of Biochemistry, University of Glasgow, U.K.
Young
P
P
Houslay
M D
MD
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010449:Peptide Mapping; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases