Wortmannin inhibits insulin-induced Ras and mitogen-activated protein kinase activation related to adipocyte differentiation in 3T3-L1 fibroblasts.
Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), inhibited adipocyte differentiation of 3T3-L1 fibroblasts induced by insulin/dexamethasone/IBMX (hormones/IBMX). Insulin as a key factor in the process of the adipocyte differentiation activated PI 3-kinase, Ras protein, and mitogen-activated protein kinase (MAP kinase, ERK) in 3T3-L1 fibroblasts. Pretreatment with wortmannin almost completely suppressed all these activations. These findings suggest that the sequential activation of PI 3-kinase, Ras protein, and MAP kinase is involved in the insulin signaling pathway(s) during differentiation by hormones/IBMX and in consequence of the inhibition of PI 3-kinase by wortmannin, the activation of Ras protein and MAP kinase which acts downstream of PI 3-kinase is suppressed and results in the inhibition of adipocyte differentiation.
Uehara
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Tokumitsu
Y
Y
Nomura
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation; D004789:Enzyme Activation; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology*; D051379:Mice; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077191:Wortmannin; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000730:Androstadienes; D007328:Insulin; D007329:Insulin Antagonists; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D005954:Glucosephosphate Dehydrogenase; D011494:Protein Kinases; D018631:ras Proteins; D000077191:Wortmannin