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New Triterpenoid Compounds stimulates Glucose Uptake Through IRS‐1‐Akt and Erk1/2‐GLUT4 Pathways in C2C12 myotubes
Author(s) -
Han JooHui,
Zhou Wei,
Na MinKyun,
Myung ChangSeon
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb523
Subject(s) - glut4 , glucose uptake , protein kinase b , insulin receptor , glucose transporter , glycogen synthase , insulin , medicine , snf3 , irs1 , myogenesis , endocrinology , gsk 3 , chemistry , biochemistry , biology , insulin resistance , skeletal muscle , signal transduction
Regulation of blood glucose levels within normal range is important for treating diabetes mellitus and one of the strategies is improving glucose uptake into insulin‐sensitive tissues, including skeletal muscle and adipose tissues. The present study has investigated the effect of new triterpenoid compounds on glucose uptake in C2C12 myotubes and in clarifying the underlying molecular mechanism, focusing on glucose uptake related insulin pathways. To evaluate the activity of triterpenoid compounds 1 and 2 , we examined glucose uptake ability and GLUT4 translocation in C2C12 myotubes. Compounds 1 and 2 significantly increased basal‐and insulin‐stimulated glucose uptake and GLUT4 translocation from cytoplasm to plasma membrane in C2C12 myotubes. Both compounds stimulated the insulin‐dependent pathway, insulin receptor substrate (IRS)‐1, protein kinase B (Akt), glycogen synthase kinase (GSK)‐3β and extracellular signal‐regulated kinase (Erk) 1/2 phosphorylation. But insulin‐independent pathway, which is 5′ adenosine monophosphate‐activated protein kinase (AMPK), acetyl‐CoA carboxylase (ACC) was not affected. Inhibition of signal activation using Akt inhibitor, triciribine, or Erk1/2, U0126 decreased the ability of both compounds to enhance basal‐ and insulin‐stimulated glucose uptake. These results indicate that compounds 1 and 2 activate both IRS‐1/Akt and Erk1/2 pathways and subsequently stimulate GLUT4 translocation, leading to increase glucose uptake activity in C2C12 myotubes. These findings supports the use of triterpenoid compounds in the regulation of blood glucose level and increase insulin sensitivity.