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Berberine Regulated Gck, G6pc, Pck1 and Srebp-1c Expression and Activated AMP-activated Protein Kinase in Primary Rat Hepatocytes
International Journal of Biological Sciences (2011)
  • Yuebin Yuebin
  • Yan Zhang
  • Rui Li
  • Wei Chen
  • Yang Li
  • Guoxun Chen
Abstract

The effects of hormonal and dietary stimuli on hepatic glucose and lipid homeostasis include regulation of gene expression. Berberine, an effective compound in certain Chinese medicinal herbs, has been reported to lower plasma glucose and lipid levels in diabetic and hypercholesterolemic patients. We hypothesized that it may affect the expression of hepatic genes involved in glucose and lipid metabolism. The effects of berberine hydrochloride on viability, gene expression, and activation of AMP activated protein kinase (AMPK) in primary hepatocytes from Sprague-Dawley (SD), Zucker lean (ZL) or fatty (ZF) rats were examined with MTT assay, real-time PCR, and western blotting, respectively. Berberine hydochloride at 50 µM or higher caused cytotoxic effects on hepatocytes. In SD and ZL hepatocytes, it induced Gck and suppressed G6pc expression at 10 and 25 µM, but not as potent as 1 nM insulin. Its effects on Pck1, and insulin-regulated Gck and G6pc expression depended on the hepatocyte sources and the dosage used. In ZF hepatocytes, it increased Gck, and suppressed Pck1 and G6pc expression without insulin. Its effects on Gck and G6pc, but not Pck1 expression, were additive with insulin. Berberine hydrochloride at 25 µM attenuated insulin-suppressed Pck1 (ZL/ZF cells), and insulin-induced Srebp-1c expression (SD/ZL/ZF cells), suggesting modulation of insulin action. Berberine hydrochloride did not alter these genes' mRNA stability. Its treatment caused a dose-dependent increase of phosphorylation of AMPKα, and its substrate, acetyl-CoA carboxylase, in primary hepatocytes. We conclude that berberine hydrochloride regulated the transcription of hepatic genes involved in glucose and fatty acid metabolism.

Keywords
  • Berberine,
  • insulin,
  • primary hepatocytes,
  • Zucker fatty rats,
  • gene expression
Publication Date
2011
Citation Information
Yuebin Yuebin, Yan Zhang, Rui Li, Wei Chen, et al.. "Berberine Regulated Gck, G6pc, Pck1 and Srebp-1c Expression and Activated AMP-activated Protein Kinase in Primary Rat Hepatocytes" International Journal of Biological Sciences Vol. 7 Iss. 5 (2011)
Available at: http://works.bepress.com/guoxun_chen/18/