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Molecular Mechanisms of Angiotensin II (ANG II)‐induced Insulin Resistance in Rat Aortic Vascular Smooth Muscle Cells (VSMC)
Author(s) -
Ketsawatsomkron Pimonrat,
BanesBerceli Amy K.,
Marrero Mario B
Publication year - 2006
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.20.5.a1172-b
Subject(s) - insulin resistance , medicine , phosphorylation , endocrinology , insulin receptor , tyrosine phosphorylation , angiotensin ii , insulin , protein tyrosine phosphatase , signal transduction , insulin receptor substrate , vascular smooth muscle , protein kinase b , chemistry , microbiology and biotechnology , biology , receptor , smooth muscle
Insulin resistance is an underlying factor of the pathogenesis of type 2 diabetes and its vascular complications. Recent evidence suggests that crosstalk between ANG II and insulin signaling pathways in VSMC contributes to the development of insulin resistance via the dephosphorylation of the IR and/or increases in serine phosphorylation of IRS‐1. We recently reported that ANG II inhibits insulin's activation of its receptor and IRS‐1 via activation of the tyrosine phosphatase PTP‐1B. Here, we tested the hypothesis that ANG II blocks the anti‐mitogenic pathways while enhancing the mitogenic pathways stimulated by insulin via activation of PTP‐1B. Utilizing standard western techniques we found that ANG II significantly inhibited insulin‐induced phosphorylation of tyrosine 608 of IRS‐1 and phosphorylation of serine 473 of Akt, a downstream member the insulin‐induced anti‐mitogenic pathway. On the other hand, ANG II enhanced the insulin‐induced activation of p42/p44 MAPK, a mitogenic pathway. Finally, we observed that PTP‐1B is involved in the augmentation by insulin on the ANG II‐induced VSMC growth. Therefore, we conclude that ANG II modulates both anti‐mitogenic and mitogenic pathways stimulated by insulin perhaps via the activation of PTP‐1B. NIH Grants HL58139, DK50268 (MBM), AHA SDG (ABB).