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Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States

¹ Department of Biological Sciences, Seoul National University, Seoul, Korea
² Research Center for Cellulomics, Seoul, Korea
³ Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
⁴ Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China
⁵ Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea

Address correspondence and reprint requests to Jae B. Kim, PhD, Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul, Korea. E-mail: jaebkim{at}snu.ac.kr; or David E. James, PhD, DiabetesObesity Research Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, Sydney, New South Wales 2010, Australia. E-mail: d.james{at}garvan.org.au

Abbreviations: AICAR, 5-aminoimidazole-4-carboxamide riboside; AMPK, AMP-activated protein kinase; DMEM, Dulbecco’s modified Eagle’s medium; FAS, fatty acid synthase; MAPK, mitogen-activated protein kinase; PI, phosphatidylinositol; PPAR, peroxisome proliferator–activated receptor; TZD, thiazolidinedione; UCP, uncoupling protein; WAT, white adipose tissue

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat–fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase–independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.

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