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The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?

Céline Saint-Laurent1,2, Laurène Mazeyrie1, Mylène Tajan1

  • 1RESTORE Research Center, Université de Toulouse, Institut National de la Santé Et de la Recherche Médicale 1301, Centre National de la Recherche Scientifique 5070, Etablissement Français du Sang, Ecole Nationale Vétérinaire de Toulouse, 31100 Toulouse, France.

Biomedicines
|September 23, 2022
PubMed

Insights

SHP2 (SH2 containing protein tyrosine phosphatase 2) is crucial for cell signaling and homeostasis. Its dysregulation links to insulin resistance, suggesting therapeutic targeting benefits.

Area of Science:

  • Molecular biology and cell signaling
  • Endocrinology and metabolic diseases
  • Pharmacology and drug development

Background:

  • SHP2 (SH2 containing protein tyrosine phosphatase 2) is a key phosphatase involved in fundamental signaling pathways.
  • SHP2 plays critical roles in development, homeostasis, and its dysregulation is linked to various pathologies.
  • Previous research indicates SHP2's involvement in glucose homeostasis and insulin resistance, with potential therapeutic implications.

Purpose of the Study:

  • To review the molecular, cellular, and physiological functions of SHP2.
  • To explain the pathophysiological impact of SHP2 dysfunctions.
  • To discuss SHP2's dual role in insulin resistance and the potential of its pharmacological modulation.

Main Methods:

  • Literature review synthesizing existing studies on SHP2.
  • Analysis of data from cellular, tissue-specific, and integrated systems models.
  • Discussion of pharmacological approaches targeting SHP2.

Main Results:

  • SHP2 is essential for normal physiological functions but its dysregulation leads to pathological outcomes.
  • Conflicting evidence exists regarding SHP2's role in insulin resistance from different model systems.
  • Recent integrated systems data suggest SHP2 promotes insulin resistance, supporting inhibition as a therapeutic strategy.

Conclusions:

  • SHP2 is a critical regulator of cellular signaling with significant physiological and pathological roles.
  • The precise role of SHP2 in insulin resistance is complex, with recent evidence favoring a pro-resistance function.
  • Pharmacological inhibition of SHP2 presents a potential therapeutic avenue for insulin resistance, though its potency and limitations require further investigation.
Keywords:
Noonan syndromeSH2 containing protein tyrosine phosphatase 2inflammationinsulin resistancemacrophage

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