title: Insulin stimulates expression of the pyruvate kinase M gene in 3T3-L1 adipocytes.
abstract: M2-type pyruvate kinase (M2-PK) mRNA is produced from the PKM gene by an alternative RNA splicing in adipocytes. We found that insulin increased the level of M2-PK mRNA in 3T3-L1 adipocytes in both time- and dose-dependent manners. This induction did not require the presence of glucose or glucosamine in the medium. The insulin effect was blocked by pharmacological inhibitors of insulin signaling pathways such as wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), and PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase. A stable reporter expression assay showed that the promoter activity of an about 2.2-kb 5'-flanking region of the rat PKM gene was stimulated by insulin, but the extents of these stimulations were lower than those of the mRNA stimulation. Thus, we suggest that insulin increases the level of M2-PK mRNA in adipocytes by acting at transcriptional and post-transcriptional levels through signaling pathways involving both PI3K and MAPK kinase.
authors.affiliation: Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Chikusa.ku, Nagoya 464-8601, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Asai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Keng
authors.forename: Tamio
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D041721:3T3-L1 Cells / Q000201:enzymology*; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects*; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D020935:MAP Kinase Signaling System; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011770:Pyruvate Kinase / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D011770:Pyruvate Kinase; D005947:Glucose; D005944:Glucosamine