Mechanism of action of brazilin on gluconeogenesis in isolated rat hepatocytes

• Published in: Planta medica Vol. 70; no. 8; pp. 740 - 744
• Main Authors: Won, H.S, Lee, J, Khil, L.Y, Chae, S.H, Ahn, M.Y, Lee, B.H, Chung, J.H, Kim, Y.C, Moon, C.K
• Format: Journal Article
• Language: English
• Published: Germany 01.08.2004
• Subjects: 3-hydroxybutyric acid; acetoacetic acid; animal models; Animals; Benzopyrans - administration & dosage; Benzopyrans - pharmacology; Benzopyrans - therapeutic use; biosynthesis; brazilin; Caesalpinia sappan; calcium; chemical structure; culture media; cultured cells; cyclic AMP; Diabetes Mellitus - pathology; disease models; Disease Models, Animal; free fatty acids; gluconeogenesis; Gluconeogenesis - drug effects; Glucose - biosynthesis; glycemic effect; hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; ketogenesis; ketone bodies; Male; medicinal plants; noninsulin-dependent diabetes mellitus; phytochemicals; Phytotherapy; Plants, Medicinal; Rats; Rats, Sprague-Dawley; signal transduction
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-2004-827205

The present study was undertaken to investigate the mechanism of action of brazilin on gluconeogenesis and ketogenesis in isolated rat hepatocytes and to elucidate the hypoglycemic mechanism of brazilin. Brazilin decreased gluconeogenesis at 100 micro M in hepatocytes isolated from diabetic rats. Brazilin also decreased basal and glucagon-induced gluconeogenesis in hepatocytes from normal rats. Fatty acids (octanoate or oleate)-induced gluconeogenesis was significantly reduced by brazilin, but ketogenesis was not influenced. The depletion of extracellular or intracellular calcium decreased gluconeogenesis in calcium-depleted media. Brazilin lowered dibutyryl cAMP (Bt2cAMP)-induced gluconeogenesis and the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) level in glucagon-treated hepatocytes. It was also found that brazilin does not require calcium for inhibition of gluconeogenesis, but may inhibit the down-stream of cAMP signaling pathways. These data suggest that a decreased gluconeogenic flux in hepatocytes might at least partly contribute to the hypoglycemic effects of brazilin.