Curcumin Activates AMPK and SuppressesGluconeogenic Gene Expression in Hepatoma Cells

Curcumin, a polyphenolic natural yellow pigment of turmeric, isolated from the rhizome of the plant Curcuma longa, has been used in Asian cuisine for several hundred years without major side effects. Several reports demonstrate its strong anti-inflammatory, anti-oxidant, anti-cancer, and anti-diabetic effects [1–3]. The goal of this study was to identify potential mechanisms that may mediate curcumin's anti-diabetic effects. The proximal and distal targets of insulin action, assayed by insulin receptor activation and 2-deoxy glucose uptake assay were not altered in either basal or insulin-stimulated condition. Curcumin did not alter either alpha-glucosidase or dipeptityl peptidase-4 activity, key enzymes involved in modulating blood glucose levels. Curcumin treatment was also without effect on PPARgamma activation and adipogenesis in human primary preadipocytes. Similarly, curcumin treatment did not ameliorate steatosis in oleic acid-treated human hepatoma Hep3B and rat hepatoma H4IIE cells. Interestingly, curcumin treatment significantly suppressed hepatic gluconeogenic gene expression, as measured by real-time quantitative PCR in H4IIE cells. Curcumin treatment (20µM) significantly decreased dexamethasone-induced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in H4IIE cells. Curcumin treatment (20µM) also resulted in significant activation of AMP-activated protein kinase (AMPK) and phosphorylation of its downstream target, acetyl CoA carboxylase (ACC). These findings suggest that curcumin's anti-diabetic effects may be mediated by suppression of hepatic gluconeogenesis via AMPK activation, without the activation of insulin signaling or the enhancement of insulin-stimulated glucose uptake. Acknowledgements: Funding from the Alabama Agricultural Initiatives Program and the Diabetes Action Research and Education Foundation (awarded to S.T.M.) is gratefully acknowledged. References: [1] Surh, YJ, Chun KS (2007) Adv Exp Med Biol, 595: 149–172. [2] Menon VP, Sudheer AR (2007) Adv Exp Med Biol, 595: 105–125. [3] Pari L, Murugan P (2007) Renal Failure 29: 881–889.