Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo.
Many active components derived from edible natural resources such as plant extracts have recently attracted attention for their potential use as functional foods or drugs for preventing and treating metabolic diseases such as diabetes. To obtain a novel modulator of glucose metabolism, we conducted screening of a small compound library in cultured L6 myotubes. We identified nepodin that stimulated glucose uptake dose-dependently in differentiated L6 myotubes. The stimulatory effect of nepodin on glucose uptake was abrogated by a 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, nepodin stimulated the phosphorylation of AMPK. Nepodin also stimulated the translocation of GLUT4 to the plasma membrane in L6 myoblasts transfected with a Glut4 cDNA-coding vector and in differentiated L6 myotubes. In in vivo study, nepodin suppressed the increases in fasting blood glucose levels and improved the glucose intolerance of C57BL/KsJ-db/db mice, a type 2 diabetic animal model. Nepodin rescued the impaired phosphorylation of AMPK in the skeletal muscle of db/db mice. These results suggest that nepodin has an antidiabetic effect, which is at least partly mediated by stimulation of GLUT4 translocation via AMPK activation by nepodin.
Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan.
Byung Geun
BG
Ha
Takayuki
T
Yonezawa
Myoung Jin
MJ
Son
Je Tae
JT
Woo
Shinsuke
S
Ohba
Ung-Il
UI
Chung
Kazumi
K
Yagasaki
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport; D051381:Rats; D031804:Rumex / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009281:Naphthalenes; C495694:Slc2a4 protein, rat; D000263:Adenylate Kinase; D005947:Glucose; C583965:nepodin
AMPK; GLUT4; db/db mouse; diabetes; nepodin