Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats

Biochemical and Biophysical Research Communications
Hiroaki OdaA Kakinuma

Abstract

The regulatory mechanism of phosphoenolpyruvate carboykinase (GTP) (EC 4.1.1.32) (PEPCK) gene expression and gluconeogenesis by phenobarbital (PB), which is known to induce drug-metabolizing enzymes, was investigated. Higher level of PEPCK mRNA was observed in spherical rat primary hepatocytes on EHS-gel than monolayer hepatocytes on TIC (type I collagen). We found that PB directly suppressed PEPCK gene expression in spherical hepatocytes on EHS-gel, but not in those on TIC. PB strongly suppressed cAMP-dependent induction of PEPCK gene expression. Tyrosine aminotransferase (TAT), another gluconeogenic enzyme, was induced by cAMP, but not suppressed by PB. Chronic administration of PB reduced hepatic PEPCK mRNA in streptozotocin-induced diabetic and nondiabetic rats, and PB reduced blood glucose level in diabetic rats. Increased TAT mRNA in diabetic rats was not suppressed by PB. These results indicated that PB-dependent reduction is specific to PEPCK. From pyrvate challenge test, PB suppressed the increased gluconeogenesis in diabetic rats. PEPCK gene promoter activity was suppressed by PB in HepG2 cells. In conclusion, we found that spherical hepatocytes cultured on EHS-gel are capable to respond to PB to suppress PEPCK gene e...Continue Reading

References

Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S HashimotoG Schütz
Sep 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·W H LamersH M Meisner
Jul 26, 1995·Biochemical and Biophysical Research Communications·H OdaA Kakinuma
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·A ValeraF Bosch
Jun 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D NitschG Schütz
Dec 4, 1996·Biochemical and Biophysical Research Communications·Y YoshidaA Kakinuma
Jul 1, 1994·Mechanisms of Ageing and Development·D A PodolinR S Mazzeo
Jul 29, 2009·The Journal of Biological Chemistry·Jianqi YangRichard W Hanson

❮ Previous
Next ❯

Citations

Aug 17, 2019·Current Vascular Pharmacology·Hoa Thi PhuGianfranco Pintus
Apr 6, 2019·Current Molecular Medicine·Venu SeenappaKapaettu Satyamoorthy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biosynthetic Transformations

Biosyntheic transformtions are multi-step, enzyme-catalyzed processes where substrates are converted into more complex products in living organisms. Simple compounds are modified, converted into other compounds, or joined together to form macromolecules. Discover the latest research on biosynthetic transformations here.