Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states.
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.
Lee
Yun S
YS
Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Korea.
Kim
Woo S
WS
Kim
Kang H
KH
Yoon
Myung J
MJ
Cho
Hye J
HJ
Shen
Yun
Y
Ye
Ji-Ming
JM
Lee
Chul H
CH
Oh
Won K
WK
Kim
Chul T
CT
Hohnen-Behrens
Cordula
C
Gosby
Alison
A
Kraegen
Edward W
EW
James
David E
DE
Kim
Jae B
JB
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000627:therapeutic use*; D002460:Cell Line; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss / Q000187:drug effects
D055372:AMP-Activated Protein Kinases; D001599:Berberine; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; D008055:Lipids; D009097:Multienzyme Complexes; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases