Genistein represses PEPCK‐C expression in an insulin‐independent manner in HepG2 cells and in alloxan‐induced diabetic mice
| Autor: | Barilin Dkhar, Donkupar Syiem, Daiahun Thabah, Kitboklang Khongsti, Bidyadhar Das, Kapaettu Satyamoorthy |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.medical_specialty endocrine system diseases medicine.medical_treatment Down-Regulation Genistein Biology Biochemistry Diabetes Mellitus Experimental Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine Alloxan medicine Animals Humans Insulin Molecular Biology nutritional and metabolic diseases AMPK Hep G2 Cells Cell Biology CRTC2 Glucose 030104 developmental biology Endocrinology Gene Expression Regulation chemistry Phosphorylation Phosphoenolpyruvate carboxykinase Phosphoenolpyruvate Carboxykinase (ATP) Signal Transduction |
| Zdroj: | Journal of Cellular Biochemistry. 119:1953-1970 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | 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 the 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 diferrent concentration of genistein in presence or absence of modulators, and the expression of cytosolic PEPCK (PEPCK-C) and the signalling 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 signalling pathways. In vivo, genistein also reduced fasting glucose levels accompanied with reduced PEPCK-C expression and increased in AMPK and ERK½ phosphorylation 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 AMPK-CRTC2 and MEK/ERK signalling pathways, which may allow a novel approach to modulate dysfunction in hepatic gluconeogenesis in T2DM. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text