Role of protein tyrosine phosphatases in the modulation of insulin signaling and their implication in the pathogenesis of obesity-linked insulin resistance



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.


Protein tyrosine phosphatase Obesity Diabetes Metabolism Insulin signaling 



Atypical protein kinase C


ATP binding cassette transporter


Acyl CoA dehydrogenases


Acyl CoA oxidase


Protein kinase A G, and C


Protein kinase B


Adaptor protein


Atypical protein kinase C


Angiotensin II subtype 2 receptor


Casitas B-lineage lymphoma


Cyclin-dependent kinase


Carcinoembryonic antigen


CEA-related adhesion molecules


Central nervous system


Caspase recruitment domain-containing protein 16


Carnitine palmitoyl transferase


Cardiovascular diseases


Endoplasmic reticulum


Fatty acids


Fatty acid synthase


Free fatty acids/non-esterified FA


Forkhead transcription factor




Grb2-associated-binding protein


Glucagon-like peptide


Glucose transporter


Growth factor receptor-bound protein 2


Glycogen synthase kinase 3


Insulin growth factor




Insulin receptor


Insulin receptor-related receptor


Insulin-receptor substrate


Janus kinase




Leukocyte common antigen-related (phosphatase)


Low molecular weight PTP


Mitogen activated protein kinase/Extracellular signal-regulated kinase


Muscle creatine kinase


MAPK kinase


Messenger ribonucleic acid


Mammalian TOR complex


Non-alcoholic fatty liver disease


Non-esterified fatty acids


Nitric oxide


60-kDa tyrosine phosphorylated protein


RNA polymerase II associated factor


PDH kinase or Phosphoinositide-dependent kinase


PPARγ co-activator 1


Pleckstrin homology


PH-domain leucine-rich repeat protein phosphatase


Phosphatidylinositol 3-kinase






Protein kinase B (also known as Akt)


Plasmic membrane


Protein phosphatase


Peroxisome proliferator-activated receptor


PBX-regulating protein


Phospho-tyrosine binding domain


Phosphatase with sequence homology to protein-tyrosine phosphatases and the cytoskeleton protein tensin


Protein tyrosine phosphatase


Proto-oncogene serine/threonine-protein kinase


G-protein and/or a family of related proteins discovered from rat sarcoma


Receptor-like PTP


Receptor tyrosine kinases


S6 kinase 1


Stearoyl-CoA desaturase


Src homology


SH2-domain containing proteins


2-SH2-domain containing protein tyrosine phosphatase


Soluble NSF attachment protein receptor


Son-of-sevenless exchange protein


Sterol response element binding protein


Signal transducer and activator of transcription


Serine/threonine phosphatase


Type 2 diabetes


Thousand and one amino acid kinase


T-cell PTP


Transcription factors


Tumor necrosis factor


Target of rapamycin


World Health Organization


Wingless and int-1



This review was written based on a literature search and some studies performed by the authors and that were supported by a grant from the Canadian Institutes of Health Research.

Conflict of interest

Authors declare no conflict of interest or financial relationship with the organization that sponsored some of the research described in this review article.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of MedicineCardiology Axis of the Institut Universitaire de Cardiologie et de Pneumologie de Québec (Hôpital Laval)Ste-FoyCanada
  2. 2.Cardiology Axis of the Institut Universitaire de Cardiologie et de Pneumologie de Québec (Hôpital Laval)Ste-FoyCanada

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