| Summary: | <p>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 <i>Gck</i> and suppressed <i>G6pc</i> expression at 10 and 25 µM, but not as potent as 1 nM insulin. Its effects on <i>Pck1,</i> and insulin-regulated <i>Gck</i> and <i>G6pc</i> expression depended on the hepatocyte sources and the dosage used. In ZF hepatocytes, it increased <i>Gck</i>, and suppressed <i>Pck1</i> and <i>G6pc</i> expression without insulin. Its effects on <i>Gck</i> and <i>G6pc</i>, but not <i>Pck1</i> expression, were additive with insulin. Berberine hydrochloride at 25 µM attenuated insulin-suppressed <i>Pck1</i> (ZL/ZF cells), and insulin-induced <i>Srebp-1c</i> 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.</p>
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