Mechanism of Action of Brazilin on Gluconeogenesis in Isolated Rat Hepatocytes

 

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Abstract

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 μM 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 hepatocytes and brazilin inhibited 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.

Abbreviations

STZ:streptozotocin

BSA:bovine serum albumin

SD rat:Sprague-Dawley rat

i. p.:intraperitoneal

EDTA:ethylenediaminetetraacetic acid

cAMP:adenosine 3′,5′-cyclic monophosphate

Bt2cAMP:dibutyryl cAMP

PBS:phosphate buffered saline

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Prof. Chang-Kiu Moon, Ph. D.

Department of Hygienic Chemistry

College of Pharmacy

San 56-1

Shillim-Dong

Kwanak-Gu

Seoul 151-742

Korea

Phone: +82-2-880-7843

Fax: +82-2-884-4580

Email: moonck@snu.ac.kr