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Role of Glycogen synthase kinase-3 in the etiology of Type 2 Diabetes Mellitus: A review

Author(s):

Asis Bala*, Susmita Roy, Debanjana Das, Venkatesh Marturi, Chaitali Mondal, Susmita Patra, Pallab Kanti Haldar and Gaurav Samajdar  

Abstract:


The risk of type 2 diabetes mellitus (T2DM) is increasing abundantly due to lifestyle-related obesity and associated cardiovascular problems. Presently, Glycogen synthase kinase-3 (GSK-3) has gained considerable attention from biomedical scientists to treat diabetes. Phosphorylation of GSK-3 permits a number of cellular activities like regulation of cell signaling, cellular metabolism, cell proliferation and cellular transport. Inhibiting GSK-3 activity by pharmacological intervention has become an important strategy for the management of T2DM. This review focuses on the schematic representation of fundamental GSK-3 enzymology and encompasses the GSK-3 inhibitors as a future therapeutic lead target for the management of T2DM that may significantly regulate insulin sensitivity to insulin receptor, glycogen synthesis and glucose metabolism. The various signaling mechanisms of inhibiting the GSK-3 by describing insulin signaling through Insulin Receptor Substrate (IRS-1), Phosphatidylinositol-3 Kinase (PI3K) and Protein Kinase B (PKB/ AKT) pathways that may hopefully facilitate the pharmacologist to design for antidiabetic drug evaluation model in near future have also been highlighted.

Keywords:

Type 2 diabetes mellitus, Etiology, Glycogen synthase kinase-3, Insulin sensitivity, glucose metabolism, Modern Targets.

Affiliation:

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, EPIP Campus, Hajipur, Bihar 844102, Division of Pharmacology and Toxicology, Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Road, Panihati, Sodepur, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, EPIP Campus, Hajipur, Bihar 844102, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, EPIP Campus, Hajipur, Bihar 844102, TCG Life Sciences (Chembiotek) Pvt. Ltd., Sector V, Salt Lake Electronics Complex, Kolkata, West Bengal 700091, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, West Bengal, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, West Bengal, Department of Pharmacology, Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata



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