Effect of corosolic acid on gluconeogenesis in rat liver.
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.
Yamada
Kotaro
K
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Hosokawa
Masaya
M
Fujimoto
Shimpei
S
Fujiwara
Hideya
H
Fujita
Yoshihito
Y
Harada
Norio
N
Yamada
Chizumi
C
Fukushima
Mitsuo
M
Ueda
Naoya
N
Kaneko
Tetsuo
T
Matsuyama
Futoshi
F
Yamada
Yuichiro
Y
Seino
Yutaka
Y
Inagaki
Nobuya
N
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*
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