title: Berberine stimulates glucose transport through a mechanism distinct from insulin.
abstract: Berberine exerts a hypoglycemic effect, but the mechanism remains unknown. In the present study, the effect of berberine on glucose uptake was characterized in 3T3-L1 adipocytes. It was revealed that berberine stimulated glucose uptake in 3T3-L1 adipocytes in a dose- and time-dependent manner with the maximal effect at 12 hours. Glucose uptake was increased by berberine in 3T3-L1 preadipocytes as well. Berberine-stimulated glucose uptake was additive to that of insulin in 3T3-L1 adipocytes, even at the maximal effective concentrations of both components. Unlike insulin, the effect of berberine on glucose uptake was insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and SB203580, an inhibitor of p38 mitogen-activated protein kinase. Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. Berberine did not induce Ser473 phosphorylation of Akt nor enhance insulin-induced phosphorylation of Akt. Meanwhile, the expression and cellular localization of glucose transporter 4 (GLUT4) were not altered by berberine. Berberine did not increase GLUT1 gene expression. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity. In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation. These findings suggest that berberine increases glucose uptake through a mechanism distinct from insulin, and activated adenosine monophosphate-activated protein kinase seems to be involved in the metabolic effect of berberine.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Shangquan
authors.initials: S
authors.lastname: Liu
authors.forename: Wenbin
authors.initials: W
authors.lastname: Shang
authors.forename: Guoyue
authors.initials: G
authors.lastname: Yuan
authors.forename: Fengying
authors.initials: F
authors.lastname: Li
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Tang
authors.forename: Mingdao
authors.initials: M
authors.lastname: Chen
authors.forename: Jialun
authors.initials: J
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000032:analysis; D051275:Glucose Transporter Type 4 / Q000032:analysis; D007328:Insulin / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D005419:Flavonoids; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D001599:Berberine; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000263:Adenylate Kinase; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one