Inhibition of insulin receptor phosphorylation by indomethacin.
Insulin stimulated phosphorylation of tyrosine residues by the insulin receptor kinase may be part of a signalling mechanism associated with insulin's action. We report that indomethacin inhibited the phosphorylation of the beta-subunit of the solubilized adipocyte insulin receptor. Indomethacin also inhibited several insulin-sensitive processes in intact rat adipocytes. Indomethacin (1 mM) inhibited basal phosphorylation of the beta-subunit of the solubilized insulin receptor by 60% and insulin-stimulated phosphorylation by 30%. In adipocytes, indomethacin inhibited basal 3-0-[methyl-14C]-methyl-D glucose transport by 50% (P less than 0.01), D-[6-14C]-glucose oxidation by 50% (P less than 0.01), D-[6-14C]-glucose conversion to lipid by 30% (P less than 0.01), and D-[1-14C]-glucose conversion to lipid by 60% (P less than 0.01). Similarly, indomethacin inhibited insulin-stimulated 3-0-[methyl-14C]-methyl-D-glucose transport by 75% (P less than 0.01), D-[6-14C]-glucose oxidation by 20% (P less than 0.05), D-[1-14C]-glucose oxidation by 35% (P less than 0.01), D-[6-14C] glucose conversion to lipid by 25% (P less than 0.01), and D-[1-14C] glucose conversion to lipid by 45% (P less than 0.01). In contrast, insulin binding to its receptor, basal D-[1-14C]-glucose oxidation and both basal and insulin-stimulated activation of glycogen synthase were unaffected by indomethacin. Thus, indomethacin partially inhibited autophosphorylation of the solubilized insulin receptor on tyrosine and partially inhibited some but not all of insulin's actions.(ABSTRACT TRUNCATED AT 250 WORDS)
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects*
D007328:Insulin; D006006:Glycogen Synthase; D011494:Protein Kinases; D011972:Receptor, Insulin; D005947:Glucose; D007213:Indomethacin