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

Progressive research in the past decade converges to the impact of PHLPP (Pleckstrin homology domain and leucine rich repeat protein phosphatase) in regulating the cellular metabolism through PI3K/Akt inhibition. Defects in the 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 understandings can be extended into treatment responses to facilitate targeted drug discovery for T2D and allied metabolic syndromes.

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