EXPLORING THE MULTIFACETED ROLE OF PTP IN THE MANAGEMENT OF DIABETIC COMPLICATIONS

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Published Nov 5, 2021
Amit Gupta Tapan Behl Sukhbir Singh Neelam Sharma

Abstract

Diabetes is considered as one of the centenarian diseases which is a global concern. From the recent available studies and WHO, diabetes is considered as a major stellar and world- wide issue. This disease is mainly characterized by elevation of plasma glucose level commonly called as hyperglycaemia. Diabetes mellitus is of two types namely juvenile diabetes or insulin dependent diabetes mellitus or type one diabetes and Adult onset diabetes or non-insulin dependent diabetes mellitus or type 2 diabetes. more than 90% of the diabetes cases are of type 2 diabetes mellitus which mainly occur due to resistance of insulin resulting in loss of homeostasis of glucose [1]. Therefore it has become necessary to find new and effective therapeutic anti-diabetic medications to cope with the increasing pace of this disease in global population. Initially the cases of type 2 diabetes were observed only in adult populations which were mainly due to modifications in lifestyles but recently the medical problem has become prevalent even in children. Conventional therapies provides symptomatic relief but often fail to manage diabetes in the cases of pre diabetic conditions and also provides less effective in managing diabetic complications. The therapies that are currently being used in management of this debilitating disorder are often ineffective due to resistance two insulin and also costly therefore demanding a situation to improve the therapeutics and find effective and alternative molecules which can help in management of this disease [2]. Thus, the orientation of scientist have inclined towards exploring novel therapeutic methods/pathways which can act as a double edged sword in managing diabetes and diabetes associated complications. the most versatile and fundamental mechanism to control the functioning of the cells such as cell growth its division differentiation and communication between cells is phosphorylation and dephosphorylation of proteins. The major role in transmitting extracellular responses for smooth functioning of different cells such as activation of T cells, signalling of antigen receptor in B cells and genetic expression in signalling pathways is mainly held by protein tyrosine phosphorylation. Two major opposing enzymes protein tyrosine kinase and protein tyrosine phosphatase control the cellular activity and are responsible for phosphate transfer and catalysing phosphate hydrolysis respectively. The stability of proteins can be controlled by addition or removal of phosphoryl group from proteins which generate recognition motives that are involved in protein-protein interactions and in monitoring the protein stability thereby affecting enzyme mobility. The protein tyrosine phosphatase enzyme mainly catalyse the phosphotyrosine hydrolysis with the help of specific proteins. The phosphotyrosine phosphatases can be distinguished by the presence of 1 catalytic domain of nearly 240 residues which poses high similarity in sequence. PTP family includes both tyrosine-specific (a) Cytosolic, nonreceptor forms PTP 1B, SHP-1, SHP-2 (b) Receptor-like, transmembrane forms CD45, RPTPµ, RPTPα and dual-specificity phosphatases like CDC25, Kinase-associated phosphatase, and MAP kinase phosphatase-1. And approximately 40% of sequence identity has been identified in the catalytic domain of PTB 1B proteins which aids in catalysation of the phosphorylation of tyrosine and further aids in phosphorylation of different types of peptides in proteins [3]. The levels of tyrosine phosphorylation in eucaryotic cells are mainly maintained by the catalytic domain of the PTP 1B. Upon gene mapping it was identified that the PTP 1B and PTPN 1 gene are present on the long arm of chromosome 20 in humans and chromosome 20 has been studied to be linked with the type 2 diabetes mellitus. This has led to identification of an association between type 2 diabetes mellitus and PTPN 1 at the genetic level. The PTP 1 B has therefore been identified as an attractive target management of type 2 diabetes mellitus since it is a negative regulator of insulin receptor and signalling of leptin receptor pathways. PTP 1B acts by dephosphorylation of incident receptors and leptin receptors leading to their deactivation and hence inhibitors of this enzyme can be useful therapeutic agent in management and treatment of type 2 diabetes mellitus. From the various literature published in past decade, Protein tyrosine phosphate (PTP) is considered as one of the most promising molecular pathway which is known to negatively regulate leptin and insulin levels. various PTP-1B inhibitors are in the pipeline research which have shown remarkable results in various in vitro and in vivo studies. in this article, we have summarized the role of PTP in the management of diabetic complications and recent findings regarding the PTP-1B inhibitors in targeting the molecular pathway associated in etiology of developing diabetic complications [4].

How to Cite

Gupta, A., Behl, T., Singh, S., & Sharma, N. (2021). EXPLORING THE MULTIFACETED ROLE OF PTP IN THE MANAGEMENT OF DIABETIC COMPLICATIONS. SPAST Abstracts, 1(01). Retrieved from https://spast.org/techrep/article/view/3192
Abstract 33 |

Article Details

Keywords

Protein tyrosine phosphatase; Diabetes; Diabetic complications, PTP-1B inhibitors.

References
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[4] P.K. Prabhakar, P.M. Sivakumar. Curr Pharm Des., 25 (23), 2526-39 (2019).
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