Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation.
Corosolic acid, a triterpenoid compound widely existing in many traditional Chinese medicinal herbs, has been proved to have antidiabetic effects on animal experiments and clinical trials. However, the underlying mechanisms remain unknown. Here, we investigate its cellular effects and related signaling pathway. We demonstrate that it enhances glucose uptake in L6 myotubes and facilitates glucose transporter isoform 4 translocation in CHO/hIR cells. These actions are mediated by insulin pathway activation and can be blocked by phosphatidylinositol 3-kinase (PI(3) Kinase) inhibitor wortmannin. Furthermore, Corosolic acid inhibits the enzymatic activities of several diabetes-related non-receptor protein tyrosine phosphatases (PTPs) in vitro, such as PTP1B, T-cell-PTP, src homology phosphatase-1 and src homology phosphatase-2.
Shi
Lei
L
National Center for Drug Screening, People's Republic of China.
Zhang
Wei
W
Zhou
Yue-Yang
YY
Zhang
Yi-Nan
YN
Li
Jing-Ya
JY
Hu
Li-Hong
LH
Li
Jia
J
D055372:AMP-Activated Protein Kinases; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D000077191:Wortmannin
D055372:AMP-Activated Protein Kinases; D000730:Androstadienes; D004791:Enzyme Inhibitors; D005947:Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D014315:Triterpenes; D000077191:Wortmannin; C495692:SLC2A4 protein, human; C113861:corosolic acid