Mechanism of action of Brazilin on gluconeogenesis in isolated rat hepatocytes.
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.
Won
Hyeon-Soon
HS
Department of Hygienic Chemistry, College of Pharmacy, Seoul National University, Seoul, Korea.
Lee
Jin
J
Khil
Lee-Yong
LY
Chae
Sang-Ho
SH
Ahn
Mee-Young
MY
Lee
Byung-Hoon
BH
Chung
Jin-Ho
JH
Kim
Young-Chul
YC
Moon
Chang-Kiu
CK
D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000473:pathology; D004195:Disease Models, Animal; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley
D001578:Benzopyrans; C044362:brazilin; D005947:Glucose