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  • WJPPS AUGUST ISSUE PUBLISHED
  • AUGUST 2020 Issue has been successfully launched on 1 August 2020.

Abstract

INHIBITION OF THE PROTEIN TYROSINE PHOSPHATASE- PTP1B: A POTENTIAL THERAPY FOR OBESITY, INSULIN RESISTANCE AND TYPE-2 DIABETES MELLITUS

Ashish Patel*a, T.Y.Pashab, Akhil Nagarc, Viral Patelc, Avinash Khadelac

ABSTRACT

The global epidemic of obesity and type-2 diabetes mellitus (T2DM) has highlighted the need for new therapeutic approaches. The association of insulin resistance with these disorders and the knowledge that insulin receptor signaling is mediated by tyrosine (Tyr) phosphorylation has generated great interest in the regulation of the balance between Tyr phosphorylation and dephosphorylation. Several proteins Tyr phosphatases (PTPs) have been implicated in the regulation of insulin action, with the most convincing data for PTP1B. Protein tyrosine phosphatases (PTPs) constitute a large family of enzymes which are crucial modulators of cellular phosphorylation events. Recent studies have demonstrated that loss of protein tyrosine phosphatase-1B (PTP1B) activity resulted in enhancement of insulin sensitivity in addition to decrease in susceptibility to diet-induced obesity, specific PTP1B inhibitors have been developed as therapeutic agents in type-2 diabetes and obesity and cancer also. A conformational change that is restricted to the movement of a flexible loop occurs during the catalytic cycle of the PTPases. However, the relationship between loop dynamics and enzyme catalysis remains to be established. The nature and identity of the rate-limiting step in the PTPases catalyzed reaction requires further investigation and may be dependent on the specific experimental conditions such as temperature, pH, buffer, and substrate used.

Keywords: Protein tyrosine phosphatase, Typer-2 Diabetes mellitus, Phosphorylation, obesity, Insulin, Tyrosine.


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