title: Hormonal regulation of glycolytic enzyme gene and pyruvate dehydrogenase kinase/phosphatase gene transcription.
abstract: Both glucocorticoid and insulin are known to have an anabolic effect on lipogenesis. The glycolytic pathway is a part of the lipogenic pathway in the liver, and glycolytic enzymes mediate the conversion from glucose to pyruvate, and pyruvate dehydrogenase complex (PDC) mediates the conversion from pyruvate to acetyl-CoA, the activity of which is regulated by pyruvate dehydrogenase kinases (PDKs) and phosphatases (PDPs). In this study, we surveyed the effects of glucocorticoid, insulin, and forskolin (used as a surrogate of glucagon) on the transcriptional activity of glucokinase (GK), phosphofructokinase-1 (PFK1), liver-type pyruvate kinase (LPK), and all the PDKs/PDPs isoform genes. We found that both glucocorticoid and insulin had positive effects on PFK1 and LPK, whereas on GK the two hormones showed the opposite effect. Regarding the PDKs/PDPs, glucocorticoid significantly stimulated the transcriptional activity of all PDKs, among which the effect on PDK4 was the most prominent. Insulin alone had minimal effects on PDKs, but dampened the positive effects of glucocorticoid. On PDPs, glucocorticoid and forskolin showed negative effects, whereas insulin had positive effects; insulin and glucocorticoid/forskolin antagonized each other. Altogether, our data suggest that both glucocorticoid and insulin have lipogenic effects through positive effects on PFK1 and LPK expression. However, glucocorticoid antagonizes the effect of insulin at the level of GK to maintain glucose homeostasis and that of PDKs/PDPs to facilitate gluconeogenesis. Glucagon may also enhance gluconeogenesis by inhibiting PDPs.
authors.affiliation: Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Li Feng
authors.initials: LF
authors.lastname: Zhao
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Takafumi
authors.initials: T
authors.lastname: Taguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsugita
authors.forename: Machiko
authors.initials: M
authors.lastname: Kambayashi
authors.forename: Kozo
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terada
mesh_terms: D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D006019:Glycolysis / Q000187:drug effects* / Q000235:genetics*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000235:genetics* / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D004798:Enzymes; D005938:Glucocorticoids; D006728:Hormones; D007328:Insulin; C000631432:PDK4 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D005576:Colforsin; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase