Hormonal Regulation of Glycolytic Enzyme Gene and Pyruvate Dehydrogenase Kinase/Phosphatase Gene Transcription

Endocrine Journal

Kozo HASHIMOTO¹  Li Feng ZHAO¹  Makoto TSUGITA¹  Yoshio TERADA¹  Mitsuru NISHIYAMA¹  Zhe WANG¹  Yasumasa IWASAKI¹  Machiko KAMBAYASHI¹  Takafumi TAGUCHI¹ 

[1] Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan

关键词: Glycolysis;    Pyruvate dehydrognase kinase;    Pyruvate dehydrogenase phosphatase;    Glucocorticoid;    Insulin;   

DOI  :  10.1507/endocrj.K09E-178

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(20)Cited-By(7)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.

【 授权许可】

Unknown