Protein kinase C-dependent antilipolysis by insulin in rat adipocytes.
Recently, we have shown that protein kinase C (PKC) activated by phorbol 12-myristate 13-acetate (PMA) attenuates the beta1-adrenergic receptor (beta1-AR)-mediated lipolysis in rat adipocytes. Stimulation of cells by insulin, angiotensin II, and alpha1-AR agonist is known to cause activation of PKC. In this study, we found that lipolysis induced by the beta1-AR agonist dobutamine is decreased and is no longer inhibited by PMA in adipocytes that have been treated with 20 nM insulin for 30 min followed by washing out insulin. Such effects on lipolysis were not found after pretreatment with angiotensin II and alpha1-AR agonists. The rate of lipolysis in the insulin-treated cells was normalized by the PKCalpha- and beta-specific inhibitor Gö 6976 and PKCbeta-specific inhibitor LY 333531. In the insulin-treated cells, wortmannin increased lipolysis and recovered the lipolysis-attenuating effect of PMA. Western blot analysis revealed that insulin slightly increases membrane-bound PKCalpha, betaI, and delta, and wortmannin decreases PKCbetaI, betaII, and delta in the membrane fraction. These results indicate that stimulation of insulin receptor induces a sustained activation of PKC-dependent antilipolysis in rat adipocytes.
Nakamura
Jiro
J
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki-ken, 305-8575, Japan. jnakamur@md.tsukuba.ac.jp
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000730:Androstadienes / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D004280:Dobutamine / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology; D008297:Male; D008301:Maleimides / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*; D000077191:Wortmannin
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000730:Androstadienes; D002227:Carbazoles; D002273:Carcinogens; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D007328:Insulin; D007527:Isoenzymes; D008301:Maleimides; D000804:Angiotensin II; C081021:Go 6976; D004280:Dobutamine; C099154:ruboxistaurin; C049763:CGP 20712A; D011972:Receptor, Insulin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D005990:Glycerol; D000077191:Wortmannin