TITLE

Berberine Suppresses Hepatic Glucose Output and Improves Insulin Signaling in Hepatocytes

AUTHOR(S)
Leng, Sanhua; Wenshuo Zhang; Liberman, Ziva; Eldar-Finkelman, Hagit; Xiao Jian Sun
PUB. DATE
June 2007
SOURCE
Diabetes;Jun2007 Supplement 1, Vol. 56, pA334
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Berberine is a natural plant-derived alkaloid with anti-diarrheal, antimicrobial, antioxidant, and hepatoprotective properties. It has been used in its purified form for over 20 years in the treatment of many ailments, with particular success in the amelioration of diarrheal diseases. Recently, it has been observed that berberine may also have antidiabetic effects. This compound has been shown to have glucose, insulin, triglyceride, and cholesterol lowering effects in various diabetic animal models. Exactly how berberine exerts its glucose-lowering effect is not known. The liver is the major organ which produces glucose during fasting and thus plays a critical role in the induction and progression of insulin resistance and diabetes. Here, we report that berberine has profound effects on glucose metabolism in primary mouse hepatocytes. Berberine reduced hepatic glucose output (HGO) in a dose-dependent manner, with maximal effects seen at 4µM. In primary hepatocytes, berberine inhibited both basal and forskolin-stimulated HGO. AICAR and metformin had similar effects, but at much higher doses when compared to berberine (0.5mM and 1mM, respectively). Like AICAR and metformin, berberine activated AMP-activated protein kinase (AMPK). Interestingly, with respect to HGO, compound C -an inhibitor of AMPK- did not block the effect of berberine and metformin, although it completely abrogated that of AICAR. The consequences of berberine on insulin signaling were also analyzed both in a liver cell line (H2.35) and in primary mouse hepatocytes. Berberine increased the mobility of IRS-1/2 on PAGE-gel, indicating a reduction in serine/threonine phosphorylation. Consequently, pretreatment of cells with berberine augmented insulin-induced tyrosine phosphorylation of IRS-1/2, as well as downstream phosphorylation of ERK-1/2; these effects were abolished by compound C. In summary, our data indicates that berberine potently suppresses HGO via an AMPK-independent mechanism while enhancing insulin signaling at the level of IRS-1/2 and ERK-1/2 in an AMPK-dependent manner. The insulin-sensitizing, glucopenic, and hypolipidemic effects of berberine, along with an established history of safe use, suggest that it may be a viable treatment for insulin resistance and related pathologies.
ACCESSION #
25821594

 

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics