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Sensing the insulin signaling pathway with an antibody array
Author(s) -
He HuaJun,
Zong Yaping,
Bernier Michel,
Wang Lili
Publication year - 2009
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200900020
Subject(s) - insulin receptor , insulin resistance , irs2 , insulin receptor substrate , signal transduction , protein kinase b , insulin , microbiology and biotechnology , pten , irs1 , biology , protein kinase c , cell signaling , kinase , chemistry , pi3k/akt/mtor pathway , endocrinology
The development of insulin resistance and type 2 diabetes is determined by various factors, including defects within the insulin signaling pathway. Mediators of insulin resistance operate through activation of various protein kinase C isoforms, IκB kinase β (IKKβ), and/or c‐Jun N‐terminal kinase, and subsequent inhibition of the proximal insulin signaling pathway via the insulin receptor substrate 1 and Akt. These mechanisms are still largely unresolved because of the complexity of the molecular events. In this study, an expression and activation state profiling of multiple known key signaling biomolecules involved in insulin metabolic and mitogenic signaling pathways was evaluated using a phosphospecific antibody array platform. The results of the arrayed antibodies were verified by the multiplexed bead array assay and conventional Western blot analysis, and confirmed the well‐known inhibitory effects of phorbol esters on insulin signaling pathway activation. Of interest, the increase in protein kinase C signaling responses with phorbol esters was associated with activation of the lipid phosphatase PTEN and a 27 kDa HSP. Thus, this insulin signaling antibody array provides a powerful and effective way to investigate the mechanism of insulin resistance and likely assist the development of innovative therapeutic drugs for type 2 diabetes.