title: Effect of corosolic acid on gluconeogenesis in rat liver.
abstract: Corosolic acid (CRA), an active component of Banaba leaves (Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20-100 microM) dose-dependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA.
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: Kotaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Masaya
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Hideya
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Fujita
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.forename: Chizumi
authors.initials: C
authors.lastname: Yamada
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Fukushima
authors.forename: Naoya
authors.initials: N
authors.lastname: Ueda
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kaneko
authors.forename: Futoshi
authors.initials: F
authors.lastname: Matsuyama
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; D002250:Carbon Radioisotopes; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005635:Fructosediphosphates / Q000096:biosynthesis; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000096:biosynthesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D028521:Musa / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D005635:Fructosediphosphates; D007546:Isoquinolines; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014315:Triterpenes; D019344:Lactic Acid; C027652:fructose 2,6-diphosphate; C113861:corosolic acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005952:Glucose-6-Phosphatase; D005947:Glucose; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide