PHLPP: a putative cellular target during insulin resistance and type 2 diabetes

    1. Poonam Kakkar1,2,3
    1. 1Herbal Research Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, India
    2. 2Babu Banarasi Das University, BBD City, Lucknow, India
    3. 3Academy of Scientific and Innovative Research, CSIR-IITR, Lucknow, India
    1. Correspondence should be addressed to P Kakkar; Email: pkakkar{at}iitr.res.in

    Abstract

    Progressive research in the past decade converges to the impact of PHLPP in regulating the cellular metabolism through PI3K/AKT inhibition. Aberrations in PKB/AKT signaling coordinates with impaired insulin secretion and insulin resistance, identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we discuss the impact of PHLPP isoforms in insulin signaling and its associated cellular events including mitochondrial dysfunction, DNA damage, autophagy and cell death. The article highlights the plausible molecular targets that share the role during insulin-resistant states, whose understanding can be extended into treatment responses to facilitate targeted drug discovery for T2D and allied metabolic syndromes.

    Keywords
    • Received 22 March 2017
    • Accepted 20 April 2017
    • Made available online as an Accepted Preprint 20 April 2017
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