Inhibition of phosphoenolpyruvate carboxykinase gene expression by metformin in cultured hepatocytes

Chinese Medical Journal

Volumn 115, Issue 12, 2002, Pages 1843-1848

  Yuan, Li ^a   Ziegler, Reinhard ^b   Hamann, Andreas ^b  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

Gluconeogenesis; Hepatocyte; Insulin; Metformin; Phosphoenolpyruvate carboxykinase; Signal transduction

Indexed keywords

ANTIDIABETIC AGENT; CYCLIC AMP; DEXAMETHASONE; GLUCOSE; INSULIN; MESSENGER RNA; METFORMIN; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); UO 126; WORTMANNIN;

ANIMAL CELL; ARTICLE; CELL CULTURE; CELL STIMULATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE INTERACTION; GLUCONEOGENESIS; HEPATOMA CELL; INHIBITION KINETICS; LIVER CELL; NONHUMAN; NORTHERN BLOTTING; RAT; SIGNAL TRANSDUCTION; TIME;

EID: 0036958167     PISSN: 03666999     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (15)

1. Hanson RW, Reshef L. Regulation of phosphoenolpyruvate carboxykinase, (GTP) gene expression. Annu Rev Biochem 1997;66:581-611.
2. Sun Y, Liu S, Ferguson S, et al. Phosphoenolpyruvate carboxykinase over-expression selectively attenuates insulin signaling and hepatic insulin sensitivity in transgenic mice. J Biol Chem 2002;277:23301-23307.
3. Bergman RN. New concepts in extracellular signaling for insulin action: the single gateway hypothesis. Recent Prog Horm Res 1997;52:359-387.
4. Sutherland C, O'Brien RM, Granner DK. Phosphatidylinositol 3-kinase, but not p7O/p85 ribosomal S6 protein kinase, is required for the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin. Dissociation of signaling pathways for insulin and phorbol ester regulation of PEPCK gene expression. J Biol Chem 1995;270:15501-15506.
5. O'Brien RM, Granner DK. Regulation of gene expression by insulin. Physiol Rev 1996;76:1109-1161.
6. Favata MF, Horiuchi KY, Manos EJ, et al. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 1998;273:18623-18632.
7. Stumvoll M, Nurjhan N, Perriello G, et al. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 1995;333:550-554.
8. Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063-2069.
9. Radziuk J, Zhang Z, Wiernsperger N, et al. Effects of metformin on lactate uptake and gluconeogenesis in the perfused rat liver. Diabetes 1997;46:1406-1413.
10. Mithieux G, Guignot L, Bordet JC, et al. Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet. Diabetes 2002;51: 139-143.
11. Large V, Beylot M. Modifications of citric acid cycle activity and gluconeogenesis in streptozotocin-induced diabetes and effects of metformin. Diabetes 1999;48:1251-1257.
12. Sutherland C, Waltner-Law M, Gnudi L, et al. Activation of the ras mitogen-activated protein kinase-ribosomal protein kinase pathway is not required for the repression of phosphoenolpyruvate carboxykinase gene transcription by insulin. J Biol Chem 1998; 273:3198-3204.
13. Agati JM, Yeagley D, Quinn PG. Assessment of the roles of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase B, and protein kinase C in insulin inhibition of cAMP-induced phosphoenolpyruvate carboxykinase gene transcription. J Biol Chem 1998;273:18751-18759.
14. Fulgencio JP, Kold C, Girard J, et al. Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes. Biochem Pharmacol 2001;62:439-449.
15. Yuan L, Ziegler R, Hamann A. Effect of metformin on the downregulation of insulin post-receptor signaling transduction induced by chronic hyperinsulinism in Hep G2 cells. Acta Pharmacologica Sinica 2002;23(in press).