title: Curcumin inhibits glucose production in isolated mice hepatocytes.
abstract: Curcumin is a compound derived from the spice turmeric, and is a potent anti-oxidant, anti-carcinogenic, and anti-hepatotoxic agent. We have investigated the acute effects of curcumin on hepatic glucose production. Gluconeogenesis and glycogenolysis in isolated hepatocytes, and gluconeogenetic enzyme activity after 120 min exposure to curcumin were measured. Hepatic gluconeogenesis from 1 mM pyruvate was inhibited in a concentration-dependent manner, with a maximal decrease of 45% at the concentration of 25 microM. After 120 min exposure to 25 microM curcumin, hepatic gluconeogenesis from 2mM dihydroxyacetone phosphate and hepatic glycogenolysis were inhibited by 35% and 20%, respectively. Insulin also inhibited hepatic gluconeogenesis from 1mM pyruvate and inhibited hepatic glycogenolysis in a concentration-dependent manner. Curcumin (25 microM) showed an additive inhibitory effect with insulin on both hepatic gluconeogenesis and glycogenolysis, indicating that curcumin inhibits hepatic glucose production in an insulin-independent manner. After 120 min exposure to 25 microM curcumin, hepatic glucose-6-phosphatase (G6Pase) activity and phosphoenolpyruvate carboxykinase (PEPCK) activity both were inhibited by 30%, but fructose-1,6-bisphosphatase (FBPase) was not reduced. After 120 min exposure to 25 microM curcumin, phosphorylation of AMP kinase alpha-Thr(172) was increased. Thus, the anti-diabetic effects of curcumin are partly due to a reduction in hepatic glucose production caused by activation of AMP kinase and inhibition of G6Pase activity and PEPCK activity.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masaya
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Fukuda
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nishi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Fujita
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000037:antagonists & inhibitors; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism
chemical_list: D006597:Fructose-Bisphosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D003474:Curcumin; D005947:Glucose