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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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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 Gourav Samajdar

Volume 18, Issue 3, 2022

Published on: 06 January, 2022

Article ID: e300721195147 Pages: 7

DOI: 10.2174/1573399817666210730094225

Price: $65

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.

[1]
Hernández F, Nido JD, Avila J, Villanueva N. GSK3 inhibitors and disease. Mini Rev Med Chem 2009; 9(9): 1024-9.
[http://dx.doi.org/10.2174/138955709788922647] [PMID: 19689399]
[2]
Alonso M, Martinez A. GSK-3 inhibitors: discoveries and developments. Curr Med Chem 2004; 11(6): 755-63.
[http://dx.doi.org/10.2174/0929867043455738] [PMID: 15032729]
[3]
Wadhwa P, Jain P, Jadhav HR. Glycogen synthase kinase 3 (GSK3): its role and inhibitors. Curr Top Med Chem 2020; 20(17): 1522-34.
[http://dx.doi.org/10.2174/1568026620666200516153136] [PMID: 32416693]
[4]
Leitner DR, Frühbeck G, Yumuk V, et al. Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obes Facts 2017; 10(5): 483-92.
[http://dx.doi.org/10.1159/000480525] [PMID: 29020674]
[5]
Medina M, Avila J. Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer’s disease. Curr Pharm Des 2010; 16(25): 2790-8.
[http://dx.doi.org/10.2174/138161210793176581] [PMID: 20698823]
[6]
Bhat RV, Budd Haeberlein SL, Avila J. Glycogen synthase kinase 3: A drug target for CNS therapies. J Neurochem 2004; 89(6): 1313-7.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02422.x] [PMID: 15189333]
[7]
Sutherland C. What Are the bona fide GSK3 Substrates? Int J Alzheimers Dis 2011; 2011: 505607.
[http://dx.doi.org/10.4061/2011/505607] [PMID: 21629754]
[8]
Ciaraldi TP, Nikoulina SE, Bandukwala RA, Carter L, Henry RR. Role of glycogen synthase kinase-3 α in insulin action in cultured human skeletal muscle cells. Endocrinol 2007; 148(9): 4393-9.
[http://dx.doi.org/10.1210/en.2006-0932] [PMID: 17569761]
[9]
Patel P, Woodgett JR. Glycogen synthase kinase 3: A kinase for all pathways? Current topics in developmental biology. Academic Press 2017; 123.
[10]
Henriksen EJ. Dysregulation of glycogen synthase kinase-3 in skeletal muscle and the etiology of insulin resistance and type 2 diabetes. Curr Diabetes Rev 2010; 6(5): 285-93.
[http://dx.doi.org/10.2174/157339910793360888] [PMID: 20594161]
[11]
Arfeen M, Bharatam PV. Design of glycogen synthase kinase-3 inhibitors: an overview on recent advancements. Curr Pharm Des 2013; 19(26): 4755-75.
[http://dx.doi.org/10.2174/1381612811319260007] [PMID: 23260024]
[12]
Hermida MA, Dinesh Kumar J, Leslie NR. GSK3 and its interactions with the PI3K/AKT/mTOR signalling network. Adv Biol Regul 2017; 65: 5-15.
[http://dx.doi.org/10.1016/j.jbior.2017.06.003] [PMID: 28712664]
[13]
Wagman AS, Johnson KW, Bussiere DE. Discovery and development of GSK3 inhibitors for the treatment of type 2 diabetes. Curr Pharm Des 2004; 10(10): 1105-37.
[http://dx.doi.org/10.2174/1381612043452668] [PMID: 15078145]
[14]
Santos CC, Chaves R, Borges AC, Oliveira de Castro M, Costa-Junior HM. Homology-based design for selective gsk-3 peptide inhibitors: Patent applications and type 2 diabetes mellitus. Curr Signal Transduct Ther 2013; 8: 156.
[http://dx.doi.org/10.2174/15743624113086660007]
[15]
Henriksen EJ, Dokken BB. Role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Curr Drug Targets 2006; 7(11): 1435-41.
[http://dx.doi.org/10.2174/1389450110607011435] [PMID: 17100583]
[16]
Beurel Eleonore, Steven F. Grieco, Richard S. Jope. Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases. Pharmacol Ther 2015; 148: 114-31.
[17]
Cohen P, Goedert M. GSK3 inhibitors: development and therapeutic potential. Nat Rev Drug Discov 2004; 3(6): 479-87.
[http://dx.doi.org/10.1038/nrd1415] [PMID: 15173837]
[18]
Mukesh K. Pandey, Timothy R. DeGrado. Review glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics 2015; 6(4): 571-93.
[19]
ter Haar E, Coll JT, Austen DA, Hsiao H-M, Swenson L, Jain J. Structure of GSK3β reveals a primed phosphorylation mechanism.Nature Publishing Group 2001. Available from: http://structbio.nature.com [Accepted 25 April, 2001]
[20]
Mudasir M, Hoda N. GSK3 inhibitors in the therapeutic development of diabetes, cancer and neurodegeneration: Past, present and future. Curr Pharm Des 2017; 23: 4332-50.
[21]
Frame S, Daniella Z. Targeting glycogen synthase kinase-3 in insulin signaling. Expert Opin Ther Targets 2006; 10(3): 429-4.
[22]
Bradley WD, James RW. GSK-3: Tricks of the trade for a multi-tasking kinase. J Cell Sci 2003; 116: 1175-86.
[23]
Philip C, Sheelagh F. The renaissance of GSK3, nature reviews. Molecular cell biology 2001; 2
[24]
Forde JE, Dale TC. Review glycogen synthase kinase 3: A key regulator of cellular fate. Cell Mol Life Sci 2007; 64(15): 1930-44.
[25]
Ali A, Hoeflich KP, Woodgett JR. Glycogen synthase kinase-3: properties, functions, and regulation. Chem Rev 2001; 101(8): 2527-40.
[http://dx.doi.org/10.1021/cr000110o] [PMID: 11749387]
[26]
Rayasam GV, Tulasi VK, Sodhi R, Davis JA, Ray A. Glycogen synthase kinase 3: more than a namesake. Br J Pharmacol 2009; 156(6): 885-98.
[http://dx.doi.org/10.1111/j.1476-5381.2008.00085.x] [PMID: 19366350]
[27]
Kaidanovich-Beilin O, RobertWoodgett J. GSK-3: Functional insights from cell biology and animal models. Mol neurosci rev 2011; 16:4:40.
[28]
Patel P, Woodgett JR. Glycogen synthase kinase 3: A kinase for all pathways?Current Topics in Developmental Biology. Elsevier Inc. 2017; 123.
[29]
Cole A, Frame S, Cohen P. Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event. Biochem J 2004; 377(Pt 1): 249-55.
[http://dx.doi.org/10.1042/bj20031259] [PMID: 14570592]
[30]
Sutherland C. Review article what are the bona fide GSK3 substrates? Int J Alzheimers Dis 2011; 2011: 505607.
[31]
S. Frame, P. Cohen. Review article GSK3 takes centre stage more than 20 years after its discovery. Biochem J 2001; 359: 1-16.
[http://dx.doi.org/10.1042/bj3590001]
[32]
Jae-Hyeon C, Gail VWJ. Glycogen synthase kinase 3 phosphorylates. J Biol Chem 2007; 278(1): 187-93.
[http://dx.doi.org/10.1074/jbc.M206236200]
[33]
Welsh GI, Stokes CM, Wang X, et al. Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3-kinase. FEBS Lett 1997; 410(2-3): 418-22.
[http://dx.doi.org/10.1016/S0014-5793(97)00579-6] [PMID: 9237674]
[34]
Yvonne LW, Philip C, Walter B, et al. The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bε at Ser539 and the microtubule-associated protein tau at Thr212: Potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem J 2001; 355: 609-15.
[http://dx.doi.org/10.1042/bj3550609] [PMID: 11311121]
[35]
Johannessen M, Moens U. Multisite phosphorylation of the cAMP response element-binding protein (CREB) by a diversity of protein kinases. Front Biosci 2007; 12: 1814-32.
[http://dx.doi.org/10.2741/2190] [PMID: 17127423]
[36]
Ziva L, Hagit E-F. Serine 332 phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 attenuates insulin signaling. The journal of biological chemistry 2005; 280(6): 4422-8.
[http://dx.doi.org/10.1074/jbc.M410610200]
[37]
Amar S, Belmaker RH, Agam G. The possible involvement of glycogen synthase kinase-3 (GSK-3) in diabetes, cancer and central nervous system diseases. Curr Pharm Des 2011; 17(22): 2264-77.
[http://dx.doi.org/10.2174/138161211797052484] [PMID: 21736545]
[38]
Diabetes. WHO report 2020. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes
[39]
Zaccardi F, Webb DR, Yates T, Davies MJ. Pathophysiology of type 1 and type 2 diabetes mellitus: A 90-year perspective. 2016; 92(1084): 63-9.
[40]
Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 2015; 350: 1756-833.
[http://dx.doi.org/10.1136/bmj.g7607]
[41]
Karpe F, Dickmann JR, Frayn KN. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 2011; 60(10): 2441-9.
[http://dx.doi.org/10.2337/db11-0425] [PMID: 21948998]
[42]
Fang X, Zuo J, Zhou J, et al. Childhood obesity leads to adult type 2 diabetes and coronary artery diseases: A 2-sample mendelian randomization study. Medicine (Baltimore) 2019; 98(32): e16825.
[http://dx.doi.org/10.1097/MD.0000000000016825] [PMID: 31393416]
[43]
Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375(9733): 2215-22.
[http://dx.doi.org/10.1016/S0140-6736(10)60484-9] [PMID: 20609967]
[44]
MacAulay K, Woodgett JR. Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of Type 2 diabetes. Expert Opin Ther Targets 2008; 12(10): 1265-74.
[http://dx.doi.org/10.1517/14728222.12.10.1265] [PMID: 18781825]
[45]
Nikoulina SE, Ciaraldi TP, Mudaliar S, Mohideen P, Carter L, Henry RR. Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes. Diabetes 2000; 49
[46]
Vestergaard H, Bjørbaek C, Andersen PH, Bak JF, Pedersen O. Impaired expression of glycogen synthase mRNA in skeletal muscle of NIDDM patients. Diabetes 1991; 40(12): 1740-5.
[http://dx.doi.org/10.2337/diab.40.12.1740] [PMID: 1756915]
[47]
Saraswati AP, Hussaini SMA, Krishna NH, Babu BN, Kamal A. Glycogen synthase kinase-3 and its inhibitors: Potential target for various therapeutic conditions. Euro J Med Chem 2018; 144: 843-58.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.103] [PMID: 29306837]
[48]
Jongsoon L, Myung-Sunny K. The role of GSK3 in glucose homeostasis and the development of insulin resistance. Diabetes research and clinical practice 2007; 77S(2007): S49-57.
[49]
Halse R, Fryer LGD, McCormack JG, Carling D, Stephen JY. Regulation of glycogen synthase by glucose and glycogen a possible role for amp-activated protein kinase. Diabetes 2003; 52.
[50]
Darren AE, Alessl DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase 3 by insulin mediated by protein kinase B. Nature 1995; 378.
[51]
Ciaraldi TP, Carter L, Mudaliar S, Henry RR. GSK-3 and control of glucose metabolism and insulin action in human skeletal muscle. Mol Cell Endocrin J 2010; 315(1-2): 153. Available from: www.elsevier.com/locate/mce.
[52]
Henriksen EJ, Dokken BB. Role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Current Drug Targets 2006; 7(11): 1435-41.
[http://dx.doi.org/10.2174/1389450110607011435] [PMID: 17100583]
[53]
Kaidanovich O, Eldar-Finkelman H. The role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Expert Opin Ther Targets 2002; 6(5): 555-61.
[http://dx.doi.org/10.1517/14728222.6.5.555] [PMID: 12387679]
[54]
Frame S, Zheleva D. Targeting glycogen synthase kinase-3 in insulin signalling. Expert Opin Ther Targets 2006; 10(3): 429-44.
[http://dx.doi.org/10.1517/14728222.10.3.429] [PMID: 16706683]
[55]
Dokken BB, Henriksen EJ. Chronic selective glycogen synthase kinase-3 inhibition enhances glucose disposal and muscle insulin action in prediabetic obese Zucker rats. Am J Physiol Endocrinol Metab 2006; 291(2): E207-13.
[http://dx.doi.org/10.1152/ajpendo.00628.2005] [PMID: 16478771]
[56]
Moller DE. New drug targets for type 2 diabetes and the metabolic syndrome. Nature 2001; 414(6865): 821-7.
[http://dx.doi.org/10.1038/414821a] [PMID: 11742415]
[57]
McCracken E, Monica M, Shiva S. Pathophysiology of the metabolic syndrome. Clin Dermatol 2018; 36(1): 14-20.
[http://dx.doi.org/10.1016/j.clindermatol.2017.09.004] [PMID: 29241747]
[58]
Chen H, Fajol A, Hoene M, et al. PI3K-resistant GSK3 controls adiponectin formation and protects from metabolic syndrome. Proc Natl Acad Sci USA 2016; 113(20): 5754-9.
[http://dx.doi.org/10.1073/pnas.1601355113] [PMID: 27140617]

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