Insulin resistance is a major disorder that links
obesity to
type 2 diabetes mellitus (T2D). It involves defects in the
insulin actions owing to a reduced ability of
insulin to trigger key signaling pathways in major metabolic tissues. The pathogenesis of
insulin resistance involves several inhibitory molecules that interfere with the
tyrosine phosphorylation of the
insulin receptor and its downstream effectors. Among those, growing interest has been developed toward the
protein tyrosine phosphatases (
PTPs), a large family of
enzymes that can inactivate crucial signaling effectors in the
insulin signaling cascade by dephosphorylating their
tyrosine residues. Herein we briefly review the role of several
PTPs that have been shown to be implicated in the regulation of
insulin action, and then focus on the Src homology 2 (SH2) domain-containing SHP1 and SHP2
enzymes, since recent reports have indicated major roles for these
PTPs in the control of
insulin action and
glucose metabolism. Finally, the therapeutic potential of targeting
PTPs for combating
insulin resistance and alleviating T2D will be discussed.