Genistein represses PEPCK-C expression in an insulin independent manner in HepG2 cells and in alloxan-induced diabetic mice

Satyamoorthy, K (2018) Genistein represses PEPCK-C expression in an insulin independent manner in HepG2 cells and in alloxan-induced diabetic mice. Journal of Cellular Biochemistry, 119 (2). pp. 1953-1970. ISSN 1097-4644

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Abstract

Genistein has been reported to exert beneficial effects on type 2 diabetes mellitus (T2DM); however, the underlying molecular mechanisms involved therein have not been clearly elucidated. To address this question, the effect of genistein on the expression of phosphoenolpyruvate carboxykinase (PEPCK), and glucose production in HepG2 cells and in alloxan-induced diabetic mice was investigated. HepG2 cells were exposed to different concentration of genistein in presence or absence ofmodulators, and the expression of cytosolic PEPCK (PEPCK-C) and the signaling pathways was studied. Further, the biological relevance of the in vitro study was tested in alloxan-induced diabetic mice. Genistein lowered PEPCK-C expression and glucose production in HepG2 cells accompanied with increased in phosphorylation states of AMPK, MEK½, ERK½, and CRTC2. Treatment with the AMPK inhibitor (compound C) enhanced genistein-induced MEK½ and ERK½ activity indicating a potential cross-talk between the two signaling pathways. In vivo, genistein also reduced fasting glucose levels accompanied with reduced PEPCK-C expression and increased inAMPKandERK½phosphorylation states in the liver of genistein-treated alloxan-induced diabetic mice. Genistein fulfills the criteria of a suitable anti-diabetic agent by reducing glucose production and inhibiting PEPCK-C expression in HepG2 cells and also in alloxan-induced diabetic mice. These results indicate that genistein is an effective candidate for preventing T2DM through the modulation of AMPKCRTC2 and MEK/ERK signaling pathways, which may allow a novel approach to modulate dysfunction in hepatic gluconeogenesis in T2DM.

Item Type: Article
Uncontrolled Keywords: AMPK/ PKB/Akt/ MEK/ERK pathways; genistein; T2DM; PEPCK-C.
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 17 May 2018 09:40
Last Modified: 17 May 2018 09:40
URI: http://eprints.manipal.edu/id/eprint/150982

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