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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes

Author(s): Ajita Paliwal, Vartika Paliwal, Smita Jain, Sarvesh Paliwal and Swapnil Sharma*

Volume 24, Issue 7, 2024

Published on: 12 September, 2023

Page: [674 - 688] Pages: 15

DOI: 10.2174/1389557523666230823151927

Price: $65

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Abstract

The glucokinase regulator (GCKR) gene encodes an inhibitor of the glucokinase enzyme (GCK), found only in hepatocytes and responsible for glucose metabolism. A common GCKR coding variation has been linked to various metabolic traits in genome-wide association studies. Rare GCKR polymorphisms influence GKRP activity, expression, and localization. Despite not being the cause, these variations are linked to hypertriglyceridemia. Because of their crystal structures, we now better understand the molecular interactions between GKRP and the GCK. Finally, small molecules that specifically bind to GKRP and decrease blood sugar levels in diabetic models have been identified. GCKR allelic spectrum changes affect lipid and glucose homeostasis. GKRP dysfunction has been linked to a variety of molecular causes, according to functional analysis. Numerous studies have shown that GKRP dysfunction is not the only cause of hypertriglyceridemia, implying that type 2 diabetes could be treated by activating liver-specific GCK via small molecule GKRP inhibition. The review emphasizes current discoveries concerning the characteristic roles of glucokinase and GKRP in hepatic glucose metabolism and diabetes. This information has influenced the growth of directed molecular therapies for diabetes, which has improved our understanding of lipid and glucose physiology.

Keywords: Glucokinase, glucokinase regulator, glucokinase regulatory protein, glucose homeostasis, diabetes therapy, hypertriglyceridemia.

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[1]
Iynedjian, P.B. Molecular physiology of mammalian glucokinase. Cell. Mol. Life Sci., 2009, 66(1), 27-42.
[http://dx.doi.org/10.1007/s00018-008-8322-9] [PMID: 18726182]
[2]
Toyoda, Y.; Miwa, I.; Satake, S.; Anai, M.; Oka, Y. Nuclear location of the regulatory protein of glucokinase in rat liver and translocation of the regulator to the cytoplasm in response to high glucose. Biochem. Biophys. Res. Commun., 1995, 215(2), 467-473.
[http://dx.doi.org/10.1006/bbrc.1995.2488] [PMID: 7487979]
[3]
Rees, M.G.; Ng, D.; Ruppert, S.; Turner, C.; Beer, N.L.; Swift, A.J.; Morken, M.A.; Below, J.E.; Blech, I.; Mullikin, J.C.; McCarthy, M.I.; Biesecker, L.G.; Gloyn, A.L.; Collins, F.S. Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes. J. Clin. Invest., 2012, 122(1), 205-217.
[http://dx.doi.org/10.1172/JCI46425] [PMID: 22182842]
[4]
Schaftingen, E. A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate. Eur. J. Biochem., 1989, 179(1), 179-184.
[http://dx.doi.org/10.1111/j.1432-1033.1989.tb14538.x] [PMID: 2917560]
[5]
Langer, S.; Kaminski, M.T.; Lenzen, S.; Baltrusch, S. Endogenous activation of glucokinase by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is glucose dependent. Mol. Endocrinol., 2010, 24(10), 1988-1997.
[http://dx.doi.org/10.1210/me.2010-0115] [PMID: 20702580]
[6]
Chu, C.A.; Fujimoto, Y.; Igawa, K.; Grimsby, J.; Grippo, J.F.; Magnuson, M.A.; Cherrington, A.D.; Shiota, M. Rapid translocation of hepatic glucokinase in response to intraduodenal glucose infusion and changes in plasma glucose and insulin in conscious rats. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286(4), 49-4.
[http://dx.doi.org/10.1152/ajpgi.00218.2003]
[7]
Van Schaftigen, E. Glucosamine-sensitive and -insensitive detritiation of [2-3H]glucose in isolated rat hepatocytes: A study of the contributions of glucokinase and glucose-6-phosphatase. Biochem. J., 1995, 308(1), 23-29.
[http://dx.doi.org/10.1042/bj3080023] [PMID: 7755569]
[8]
Saxena, R.; Voight, B.F.; Lyssenko, V.; Burtt, N.P.; De Bakker, P.I.W.; Chen, H.; Roix, J.J.; Kathiresan, S.; Hirschhorn, J.N.; Daly, M.J.; Hughes, T.E.; Groop, L.; Altshuler, D. Genome-wide association analysis identifies loci for Type 2 diabetes and triglyceride levels. Science, 2007, 316(5829), 1331-1336.
[9]
Johansen, C.T.; Wang, J.; Lanktree, M.B.; Cao, H.; McIntyre, A.D.; Ban, M.R.; Martins, R.A.; Kennedy, B.A.; Hassell, R.G.; Visser, M.E.; Schwartz, S.M.; Voight, B.F.; Elosua, R.; Salomaa, V.; O’Donnell, C.J.; Dallinga-Thie, G.M.; Anand, S.S.; Yusuf, S.; Huff, M.W.; Kathiresan, S.; Hegele, R.A. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat. Genet., 2010, 42(8), 684-687.
[http://dx.doi.org/10.1038/ng.628] [PMID: 20657596]
[10]
Grimsby, J.; Sarabu, R.; Corbett, W.L.; Haynes, N.E.; Bizzarro, F.T.; Coffey, J.W.; Guertin, K.R.; Hilliard, D.W.; Kester, R.F.; Mahaney, P.E.; Marcus, L.; Qi, L.; Spence, C.L.; Tengi, J.; Magnuson, M.A.; Chu, C.A.; Dvorozniak, M.T.; Matschinsky, F.M.; Grippo, J.F. Allosteric activators of glucokinase: Potential role in diabetes therapy. Science, 2003, 301(5631), 370-373.
[http://dx.doi.org/10.1126/science.1084073]
[11]
Bonadonna, R.C.; Heise, T.; Arbet-Engels, C.; Kapitza, C.; Avogaro, A.; Grimsby, J.; Zhi, J.; Grippo, J.F.; Balena, R. Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J. Clin. Endocrinol. Metab., 2010, 95(11), 5028-5036.
[http://dx.doi.org/10.1210/jc.2010-1041] [PMID: 20739378]
[12]
De Ceuninck, F.; Kargar, C.; Ilic, C.; Caliez, A.; Rolin, J.O.; Umbdenstock, T.; Vinson, C.; Combettes, M.; de Fanti, B.; Harley, E.; Sadlo, M.; Lefèvre, A.L.; Broux, O.; Wierzbicki, M.; Fourquez, J.M.; Perron-Sierra, F.; Kotschy, A.; Ktorza, A. Small molecule glucokinase activators disturb lipid homeostasis and induce fatty liver in rodents: A warning for therapeutic applications in humans. Br. J. Pharmacol., 2013, 168(2), 339-353.
[http://dx.doi.org/10.1111/j.1476-5381.2012.02184.x] [PMID: 22925001]
[13]
Meininger, G.E.; Scott, R.; Alba, M.; Shentu, Y.; Luo, E.; Amin, H.; Davies, M.J.; Kaufman, K.D.; Goldstein, B.J. Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes. Diabetes Care, 2011, 34(12), 2560-2566.
[http://dx.doi.org/10.2337/dc11-1200] [PMID: 21994424]
[14]
Christesen, H.B.T.; Jacobsen, B.B.; Odili, S.; Buettger, C.; Cuesta-Munoz, A.; Hansen, T.; Brusgaard, K.; Massa, O.; Magnuson, M.A.; Shiota, C.; Matschinsky, F.M.; Barbetti, F. The second activating glucokinase mutation (A456V): Implications for glucose homeostasis and diabetes therapy. Diabetes, 2002, 51(4), 1240-1246.
[http://dx.doi.org/10.2337/diabetes.51.4.1240] [PMID: 11916951]
[15]
Sarabu, R.; Taub, R.; Grimsby, J. Glucokinase activation–a strategy for T2D therapy: Recent developments. Drug Discov. Today Ther. Strateg., 2007, 4(2), 111-115.
[http://dx.doi.org/10.1016/j.ddstr.2007.10.009]
[16]
Iynedjian, P.B. Mammalian glucokinase and its gene. Biochem. J., 1993, 293(1), 1-13.
[http://dx.doi.org/10.1042/bj2930001] [PMID: 8392329]
[17]
Cullen, K.S.; Al-Oanzi, Z.H.; O’Harte, F.P.M.; Agius, L.; Arden, C. Glucagon induces translocation of glucokinase from the cytoplasm to the nucleus of hepatocytes by transfer between 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase-2 and the glucokinase regulatory protein. Biochim. Biophys. Acta Mol. Cell Res., 2014, 1843(6), 1123-1134.
[http://dx.doi.org/10.1016/j.bbamcr.2014.02.006] [PMID: 24566088]
[18]
Fisher, F.M.; Maratos-Flier, E. Understanding the physiology of FGF21. Annu. Rev. Physiol., 2016, 78(1), 223-241.
[http://dx.doi.org/10.1146/annurev-physiol-021115-105339] [PMID: 26654352]
[19]
Agius, L. Hormonal and metabolite regulation of hepatic glucokinase., 2016, 36, 389-415.
[http://dx.doi.org/10.1146/annurev-nutr-071715-051145]
[20]
de la Iglesia, N.; Mukhtar, M.; Seoane, J.; Guinovart, J.J.; Agius, L. The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. J. Biol. Chem., 2000, 275(14), 10597-10603.
[http://dx.doi.org/10.1074/jbc.275.14.10597] [PMID: 10744755]
[21]
Zelent, B.; Raimondo, A.; Barrett, A.; Buettger, C.W.; Chen, P.; Gloyn, A.L.; Matschinsky, F.M. Analysis of the co-operative interaction between the allosterically regulated proteins GK and GKRP using tryptophan fluorescence. Biochem. J., 2014, 459(3), 551-564.
[http://dx.doi.org/10.1042/BJ20131363] [PMID: 24568320]
[22]
Ashton, K.S.; Andrews, K.L.; Bryan, M.C.; Chen, J.; Chen, K.; Chen, M.; Chmait, S.; Croghan, M.; Cupples, R.; Fotsch, C.; Helmering, J.; Jordan, S.R.; Kurzeja, R.J.M.; Michelsen, K.; Pennington, L.D.; Poon, S.F.; Sivits, G.; Van, G.; Vonderfecht, S.L.; Wahl, R.C.; Zhang, J.; Lloyd, D.J.; Hale, C.; St Jean, D.J., Jr Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 1. Discovery of a novel tool compound for in vivo proof-of-concept. J. Med. Chem., 2014, 57(2), 309-324.
[http://dx.doi.org/10.1021/jm4016735] [PMID: 24405172]
[23]
Hers, H.G.; Hue, L. Gluconeogenesis and related aspects of glycolysis. Annu. Rev. Biochem., 2003, 52, 617-653.
[http://dx.doi.org/10.1146/annurev.bi.52.070183.003153]
[24]
Matschinsky, F.M. Glucokinase as glucose sensor and metabolic signal generator in pancreatic β-cells and hepatocytes. Diabetes, 1990, 39(6), 647-652.
[http://dx.doi.org/10.2337/diab.39.6.647] [PMID: 2189759]
[25]
Titchenell, P.M.; Lazar, M.A.; Birnbaum, M.J. Unraveling the regulation of hepatic metabolism by insulin. Trends Endocrinol. Metab., 2017, 28(7), 497-505.
[http://dx.doi.org/10.1016/j.tem.2017.03.003] [PMID: 28416361]
[26]
Ferre, T.; Pujol, A.; Riu, E.; Bosch, F.; Valera, A. Correction of diabetic alterations by glucokinase. Proc. Natl. Acad. Sci., 1996, 93(14), 7225-7230.
[http://dx.doi.org/10.1073/pnas.93.14.7225] [PMID: 8692973]
[27]
Nissim, I.; Horyn, O.; Nissim, I.; Daikhin, Y.; Wehrli, S.L.; Yudkoff, M.; Matschinsky, F.M. Effects of a glucokinase activator on hepatic intermediary metabolism: Study with 13C-isotopomer-based metabolomics. Biochem. J., 2012, 444(3), 537-551.
[http://dx.doi.org/10.1042/BJ20120163] [PMID: 22448977]
[28]
Affourtit, C.; Alberts, B.; Barlow, J.; Carré, J.E.; Wynne, A.G. Control of pancreatic β-cell bioenergetics. Biochem. Soc. Trans., 2018, 46(3), 555-564.
[http://dx.doi.org/10.1042/BST20170505] [PMID: 29666215]
[29]
Nicholls, D.G. The pancreatic β-Cell: A bioenergetic perspective. Physiol. Rev., 2016, 96(4), 1385-1447.
[http://dx.doi.org/10.1152/physrev.00009.2016] [PMID: 27582250]
[30]
Kaufman, B.A.; Li, C.; Soleimanpour, S.A. Mitochondrial regulation of β-cell function: Maintaining the momentum for insulin release. Mol. Aspects Med., 2015, 42, 91-104.
[http://dx.doi.org/10.1016/j.mam.2015.01.004] [PMID: 25659350]
[31]
Doliba, N.M.; Qin, W.; Najafi, H.; Liu, C.; Buettger, C.W.; Sotiris, J.; Collins, H.W.; Li, C.; Stanley, C.A.; Wilson, D.F.; Grimsby, J.; Sarabu, R.; Naji, A.; Matschinsky, F.M. Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics. Am. J. Physiol. Endocrinol. Metab., 2012, 302(1), E87-E102.
[http://dx.doi.org/10.1152/ajpendo.00218.2011] [PMID: 21952036]
[32]
Matschinsky, F.M. Assessing the potential of glucokinase activators in diabetes therapy. Nat. Rev. Drug Discov., 2009, 8(5), 399-416.
[http://dx.doi.org/10.1038/nrd2850] [PMID: 19373249]
[33]
Lenzen, S. A fresh view of glycolysis and glucokinase regulation: History and current status. J. Biol. Chem., 2014, 289(18), 12189-12194.
[http://dx.doi.org/10.1074/jbc.R114.557314] [PMID: 24637025]
[34]
Baltrusch, S.; Tiedge, M. Glucokinase regulatory network in pancreatic β-Cells and Liver. Diabetes, 2006, 55(Suppl. 2), S55-S64.
[http://dx.doi.org/10.2337/db06-S008]
[35]
Schmitt, D.L.; An, S. Spatial organization of metabolic enzyme complexes in cells. Biochemistry, 2017, 56(25), 3184-3196.
[http://dx.doi.org/10.1021/acs.biochem.7b00249] [PMID: 28580779]
[36]
Sternisha, S.M.; Miller, B.G. Molecular and cellular regulation of human glucokinase. Arch. Biochem. Biophys., 2019, 663, 199-213.
[http://dx.doi.org/10.1016/j.abb.2019.01.011] [PMID: 30641049]
[37]
Bahl, V.; Lee May, C.; Perez, A.; Glaser, B.; Kaestner, K.H. Genetic activation of α-cell glucokinase in mice causes enhanced glucose-suppression of glucagon secretion during normal and diabetic states. Mol. Metab., 2021, 49, 101193.
[http://dx.doi.org/10.1016/j.molmet.2021.101193] [PMID: 33610858]
[38]
Pautsch, A.; Stadler, N.; Löhle, A.; Rist, W.; Berg, A.; Glocker, L.; Nar, H.; Reinert, D.; Lenter, M.; Heckel, A.; Schnapp, G.; Kauschke, S.G. Crystal structure of glucokinase regulatory protein. Biochemistry, 2013, 52(20), 3523-3531.
[http://dx.doi.org/10.1021/bi4000782] [PMID: 23621087]
[39]
Agius, L. Glucokinase and molecular aspects of liver glycogen metabolism. Biochem. J., 2008, 414(1), 1-18.
[http://dx.doi.org/10.1042/BJ20080595] [PMID: 18651836]
[40]
Lloyd, D.J.; St Jean, D.J., Jr; Kurzeja, R.J.M.; Wahl, R.C.; Michelsen, K.; Cupples, R.; Chen, M.; Wu, J.; Sivits, G.; Helmering, J.; Komo-rowski, R.; Ashton, K.S.; Pennington, L.D.; Fotsch, C.; Vazir, M.; Chen, K.; Chmait, S.; Zhang, J.; Liu, L.; Norman, M.H.; Andrews, K.L.; Bartberger, M.D.; Van, G.; Galbreath, E.J.; Vonderfecht, S.L.; Wang, M.; Jordan, S.R.; Véniant, M.M.; Hale, C. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature, 2013, 504(7480), 437-440.
[http://dx.doi.org/10.1038/nature12724] [PMID: 24226772]
[41]
Mokdad, A.H.; Ford, E.S.; Bowman, B.A.; Dietz, W.H.; Vinicor, F.; Bales, V.S.; Marks, J.S. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA, 2003, 289(1), 76-79.
[http://dx.doi.org/10.1001/jama.289.1.76] [PMID: 12503980]
[42]
Consoli, A. Role of liver in pathophysiology of NIDDM. Diabetes Care, 1992, 15(3), 430-441.
[http://dx.doi.org/10.2337/diacare.15.3.430] [PMID: 1559410]
[43]
Nordlie, R.C.; Foster, J.D.; Lange, A.J. Regulation of glucose production by the liver. Annu. Rev. Nutr., 1999, 19(1), 379-406.
[http://dx.doi.org/10.1146/annurev.nutr.19.1.379] [PMID: 10448530]
[44]
Iynedjian, P.B.; Jotterand, D.; Nouspikel, T.; Asfari, M.; Pilot, P.R. Transcriptional induction of glucokinase gene by insulin in cultured liver cells and its repression by the glucagon-cAMP system. J. Biol. Chem., 1989, 264(36), 21824-21829.
[http://dx.doi.org/10.1016/S0021-9258(20)88258-1] [PMID: 2557341]
[45]
Iynedjian, P.B.; Gjinovci, A.; Renold, A.E. Stimulation by insulin of glucokinase gene transcription in liver of diabetic rats. J. Biol. Chem., 1988, 263(2), 740-744.
[http://dx.doi.org/10.1016/S0021-9258(19)35415-8] [PMID: 3275657]
[46]
Kim, T.H.; Kim, H.; Park, J.M. Im, S.S.; Bae, J.S.; Kim, M.Y.; Yoon, H.G.; Cha, J.Y.; Kim, K.S.; Ahn, Y.H. Interrelationship between liver X receptor α, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, and small heterodimer partner in the transcriptional regulation of glucokinase gene expression in liver. J. Biol. Chem., 2009, 284(22), 15071-15083.
[http://dx.doi.org/10.1074/jbc.M109.006742] [PMID: 19366697]
[47]
Beer, N.L.; Tribble, N.D.; McCulloch, L.J.; Roos, C.; Johnson, P.R.V.; Orho-Melander, M.; Gloyn, A.L. The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. Hum. Mol. Genet., 2009, 18(21), 4081-4088.
[http://dx.doi.org/10.1093/hmg/ddp357] [PMID: 19643913]
[48]
Agius, L.; Stubbs, M. Investigation of the mechanism by which glucose analogues cause translocation of glucokinase in hepatocytes: Evidence for two glucose binding sites. Biochem. J., 2000, 346(2), 413-421.
[http://dx.doi.org/10.1042/bj3460413] [PMID: 10677361]
[49]
Van Schaftingen, E.; Detheux, M.; Da Cunha, M.V. Short‐term control of glucokinase activity: Role of a regulatory protein. FASEB J., 1994, 8(6), 414-419.
[http://dx.doi.org/10.1096/fasebj.8.6.8168691] [PMID: 8168691]
[50]
Detheux, M.; Vandercammen, A.; Schaftingen, E. Effectors of the regulatory protein acting on liver glucokinase: A kinetic investigation. Eur. J. Biochem., 1991, 200(2), 553-561.
[http://dx.doi.org/10.1111/j.1432-1033.1991.tb16218.x] [PMID: 1889418]
[51]
Mukhtar, M.H.; Payne, V.A.; Arden, C.; Harbottle, A.; Khan, S.; Lange, A.J.; Agius, L. Inhibition of glucokinase translocation by AMP-activated protein kinase is associated with phosphorylation of both GKRP and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2008, 294(3), R766-R774.
[http://dx.doi.org/10.1152/ajpregu.00593.2007] [PMID: 18199594]
[52]
Zhao, Y.; Wang, Y.; Zhu, W.G. Applications of post-translational modifications of FoxO family proteins in biological functions. J. Mol. Cell Biol., 2011, 3(5), 276-282.
[http://dx.doi.org/10.1093/jmcb/mjr013] [PMID: 21669942]
[53]
Park, J.M.; Kim, T.H.; Jo, S.H.; Kim, M.Y.; Ahn, Y.H. Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity. Sci. Rep., 2015, 5(1), 17395.
[http://dx.doi.org/10.1038/srep17395] [PMID: 26620281]
[54]
Vandercammen, A.; Van Schaftingen, E. Species and tissue distribution of the regulatory protein of glucokinase. Biochem. J., 1993, 294(2), 551-556.
[http://dx.doi.org/10.1042/bj2940551] [PMID: 8373368]
[55]
Farrelly, D.; Brown, K.S.; Tieman, A.; Ren, J.; Lira, S.A.; Hagan, D.; Gregg, R.; Mookhtiar, K.A.; Hariharan, N. Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: A sequestration mechanism in metabolic regulation. Proc. Natl. Acad. Sci., 1999, 96(25), 14511-14516.
[http://dx.doi.org/10.1073/pnas.96.25.14511] [PMID: 10588736]
[56]
Grimsby, J.; Coffey, J.W.; Dvorozniak, M.T.; Magram, J.; Li, G.; Matschinsky, F.M.; Shiota, C.; Kaur, S.; Magnuson, M.A.; Grippo, J.F. Characterization of glucokinase regulatory protein-deficient mice. J. Biol. Chem., 2000, 275(11), 7826-7831.
[http://dx.doi.org/10.1074/jbc.275.11.7826] [PMID: 10713097]
[57]
Slosberg, E.D.; Desai, U.J.; Fanelli, B.; St Denny, I.; Connelly, S.; Kaleko, M.; Boettcher, B.R.; Caplan, S.L. Treatment of type 2 diabetes by adenoviral-mediated overexpression of the glucokinase regulatory protein. Diabetes, 2001, 50(8), 1813-1820.
[http://dx.doi.org/10.2337/diabetes.50.8.1813] [PMID: 11473043]
[58]
Vandercammen, A.; Schaftingen, E. Competitive inhibition of liver glucokinase by its regulatory protein. Eur. J. Biochem., 1991, 200(2), 545-551.
[http://dx.doi.org/10.1111/j.1432-1033.1991.tb16217.x] [PMID: 1889417]
[59]
Bosco, D.; Meda, P.; Iynedjian, P.B. Glucokinase and glucokinase regulatory protein: Mutual dependence for nuclear localization. Biochem. J., 2000, 348(1), 215-222.
[http://dx.doi.org/10.1042/bj3480215] [PMID: 10794734]
[60]
Walker, D.G.; Holland, G. The development of hepatic glucokinase in the neonatal rat. Biochem. J., 1965, 97(3), 845-854.
[http://dx.doi.org/10.1042/bj0970845] [PMID: 5883129]
[61]
Guo, T.; Mao, Y.; Li, H.; Wang, X.; Xu, W.; Song, R.; Jia, J.; Lei, Z.; Irwin, D.M.; Niu, G.; Tan, H. Characterization of the gene expression profile of heterozygous liver-specific glucokinase knockout mice at a young age. Biomed. Pharmacother., 2012, 66(8), 587-596.
[http://dx.doi.org/10.1016/j.biopha.2012.07.002] [PMID: 23085254]
[62]
Jin, L.; Guo, T.; Li, Z.; Lei, Z.; Li, H.; Mao, Y.; Wang, X.; Zhou, N.; Zhang, Y.; Hu, R.; Zhang, X.; Niu, G.; Irwin, D.; Tan, H. Role of glucokinase in the subcellular localization of glucokinase regulatory protein. Int. J. Mol. Sci., 2015, 16(12), 7377-7393.
[http://dx.doi.org/10.3390/ijms16047377] [PMID: 25849650]
[63]
Teslovich, T.M.; Musunuru, K.; Smith, A.V.; Edmondson, A.C.; Stylianou, I.M.; Koseki, M.; Pirruccello, J.P.; Ripatti, S.; Chasman, D.I.; Willer, C.J.; Johansen, C.T.; Fouchier, S.W.; Isaacs, A.; Peloso, G.M.; Barbalic, M.; Ricketts, S.L.; Bis, J.C.; Aulchenko, Y.S.; Thorleifsson, G.; Feitosa, M.F.; Chambers, J.; Orho-Melander, M.; Melander, O.; Johnson, T.; Li, X.; Guo, X.; Li, M.; Shin Cho, Y.; Jin Go, M.; Jin Kim, Y.; Lee, J.Y.; Park, T.; Kim, K.; Sim, X.; Twee-Hee Ong, R.; Croteau-Chonka, D.C.; Lange, L.A.; Smith, J.D.; Song, K.; Hua, Zhao J.; Yuan, X.; Luan, J.; Lamina, C.; Ziegler, A.; Zhang, W.; Zee, R.Y.; Wright, A.F.; Witteman, J.C.; Wilson, J.F.; Willemsen, G.; Wichmann, H.E.; Whitfield, J.B.; Waterworth, D.M.; Wareham, N.J.; Waeber, G.; Vollenweider, P.; Voight, B.F.; Vitart, V.; Uitterlinden, A.G.; Uda, M.; Tuomilehto, J.; Thompson, J.R.; Tanaka, T.; Surakka, I.; Stringham, H.M.; Spector, T.D.; Soranzo, N.; Smit, J.H.; Sinisalo, J.; Silander, K.; Sijbrands, E.J.; Scuteri, A.; Scott, J.; Schlessinger, D.; Sanna, S.; Salomaa, V.; Saharinen, J.; Sabatti, C.; Ruokonen, A.; Rudan, I.; Rose, L.M.; Roberts, R.; Rieder, M.; Psaty, B.M.; Pramstaller, P.P.; Pichler, I.; Perola, M.; Penninx, B.W.; Pedersen, N.L.; Pattaro, C.; Parker, A.N.; Pare, G.; Oostra, B.A.; O’Donnell, C.J.; Nieminen, M.S.; Nickerson, D.A.; Montgomery, G.W.; Meitinger, T.; McPherson, R.; McCarthy, M.I.; McArdle, W.; Masson, D.; Martin, N.G.; Marroni, F.; Mangino, M.; Magnusson, P.K.; Lucas, G.; Luben, R.; Loos, R.J.; Lokki, M.L.; Lettre, G.; Langenberg, C.; Launer, L.J.; Lakatta, E.G.; Laaksonen, R.; Kyvik, K.O.; Kronenberg, F.; König, I.R.; Khaw, K.T.; Kaprio, J.; Kaplan, L.M.; Johansson, A.; Jarvelin, M.R.; Janssens, A.C.; Ingelsson, E.; Igl, W.; Kees Hovingh, G.; Hottenga, J.J.; Hofman, A.; Hicks, A.A.; Hengstenberg, C.; Heid, I.M.; Hayward, C.; Havulinna, A.S.; Hastie, N.D.; Harris, T.B.; Haritunians, T.; Hall, A.S.; Gyllensten, U.; Guiducci, C.; Groop, L.C.; Gonzalez, E.; Gieger, C.; Freimer, N.B.; Ferrucci, L.; Erdmann, J.; Elliott, P.; Ejebe, K.G.; Döring, A.; Dominiczak, A.F.; Demissie, S.; Deloukas, P.; de Geus, E.J.; de Faire, U.; Crawford, G.; Collins, F.S.; Chen, Y.D.; Caulfield, M.J.; Campbell, H.; Burtt, N.P.; Bonnycastle, L.L.; Boomsma, D.I.; Boekholdt, S.M.; Bergman, R.N.; Barroso, I.; Bandinelli, S.; Ballantyne, C.M.; Assimes, T.L.; Quertermous, T.; Altshuler, D.; Seielstad, M.; Wong, T.Y.; Tai, E.S.; Feranil, A.B.; Kuzawa, C.W.; Adair, L.S.; Taylor, H.A., Jr; Borecki, I.B.; Gabriel, S.B.; Wilson, J.G.; Holm, H.; Thorsteinsdottir, U.; Gudnason, V.; Krauss, R.M.; Mohlke, K.L.; Ordovas, J.M.; Munroe, P.B.; Kooner, J.S.; Tall, A.R.; Hegele, R.A.; Kastelein, J.J.; Schadt, E.E.; Rotter, J.I.; Boerwinkle, E.; Strachan, D.P.; Mooser, V.; Stefansson, K.; Reilly, M.P.; Samani, N.J.; Schunkert, H.; Cupples, L.A.; Sandhu, M.S.; Ridker, P.M.; Rader, D.J.; van Duijn, C.M.; Peltonen, L.; Abecasis, G.R.; Boehnke, M.; Kathiresan, S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature, 2010, 466(7307), 707-713.
[http://dx.doi.org/10.1038/nature09270] [PMID: 20686565]
[64]
Johansen, C.T.; Wang, J.; Lanktree, M.B.; McIntyre, A.D.; Ban, M.R.; Martins, R.A.; Kennedy, B.A.; Hassell, R.G.; Visser, M.E.; Schwartz, S.M.; Voight, B.F.; Elosua, R.; Salomaa, V.; O’Donnell, C.J.; Dallinga-Thie, G.M.; Anand, S.S.; Yusuf, S.; Huff, M.W.; Kathiresan, S.; Cao, H.; Hegele, R.A. An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia. Arterioscler. Thromb. Vasc. Biol., 2011, 31(8), 1916-1926.
[http://dx.doi.org/10.1161/ATVBAHA.111.226365] [PMID: 21597005]
[65]
Rees, M.G.; Gloyn, A.L. Small molecular glucokinase activators: Has another new anti-diabetic therapeutic lost favour? Br. J. Pharmacol., 2013, 168(2), 335-338.
[http://dx.doi.org/10.1111/j.1476-5381.2012.02201.x] [PMID: 22946641]
[66]
Choi, J.M.; Seo, M.H.; Kyeong, H.H.; Kim, E.; Kim, H.S. Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase. Proc. Natl. Acad. Sci., 2013, 110(25), 10171-10176.
[http://dx.doi.org/10.1073/pnas.1300457110] [PMID: 23733961]
[67]
Beck, T.; Miller, B.G. Structural basis for regulation of human glucokinase by glucokinase regulatory protein. Biochemistry, 2013, 52(36), 6232-6239.
[http://dx.doi.org/10.1021/bi400838t] [PMID: 23957911]
[68]
Veiga-da-Cunha, M.; Sokolova, T.; Opperdoes, F.; Van Schaftingen, E. Evolution of vertebrate glucokinase regulatory protein from a bacterial N -acetylmuramate 6-phosphate etherase. Biochem. J., 2009, 423(3), 323-332.
[http://dx.doi.org/10.1042/BJ20090986] [PMID: 19671048]
[69]
Anderka, O.; Boyken, J.; Aschenbach, U.; Batzer, A.; Boscheinen, O.; Schmoll, D. Biophysical characterization of the interaction between hepatic glucokinase and its regulatory protein: Impact of physiological and pharmacological effectors. J. Biol. Chem., 2008, 283(46), 31333-31340.
[http://dx.doi.org/10.1074/jbc.M805434200] [PMID: 18809676]
[70]
Bourbonais, F.J.; Chen, J.; Huang, C.; Zhang, Y.; Pfefferkorn, J.A.; Landro, J.A. Modulation of glucokinase by glucose, small-molecule activator and glucokinase regulatory protein: Steady-state kinetic and cell-based analysis. Biochem. J., 2012, 441(3), 881-887.
[http://dx.doi.org/10.1042/BJ20110721] [PMID: 22044397]
[71]
Nishimura, N.; Norman, M.H.; Liu, L.; Yang, K.C.; Ashton, K.S.; Bartberger, M.D.; Chmait, S.; Chen, J.; Cupples, R.; Fotsch, C.; Helmering, J.; Jordan, S.R.; Kunz, R.K.; Pennington, L.D.; Poon, S.F.; Siegmund, A.; Sivits, G.; Lloyd, D.J.; Hale, C.; St Jean, D.J., Jr Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N'-arylpiperazine series. J. Med. Chem., 2014, 57(7), 3094-3116.
[http://dx.doi.org/10.1021/jm5000497] [PMID: 24611879]
[72]
St Jean, D.J., Jr; Ashton, K.S.; Bartberger, M.D.; Chen, J.; Chmait, S.; Cupples, R.; Galbreath, E.; Helmering, J.; Hong, F.T.; Jordan, S.R.; Liu, L.; Kunz, R.K.; Michelsen, K.; Nishimura, N.; Pennington, L.D.; Poon, S.F.; Reid, D.; Sivits, G.; Stec, M.M.; Tadesse, S.; Tamayo, N.; Van, G.; Yang, K.C.; Zhang, J.; Norman, M.H.; Fotsch, C.; Lloyd, D.J.; Hale, C. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles. J. Med. Chem., 2014, 57(2), 325-338.
[http://dx.doi.org/10.1021/jm4016747] [PMID: 24405213]
[73]
Hong, F-T.; Norman, M.H.; Ashton, K.S.; Bartberger, M.D.; Chen, J.; Chmait, S.; Cupples, R.; Fotsch, C.; Jordan, S.R.; Lloyd, D.J.; Sivits, G.; Tadesse, S.; Hale, C.; St Jean, D.J., Jr Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 4. Exploration of a novel binding pocket. J. Med. Chem., 2014, 57(14), 5949-5964.
[http://dx.doi.org/10.1021/jm5001979] [PMID: 25001129]
[74]
Jain, S.; Bisht, A.; Verma, K.; Negi, S.; Paliwal, S.; Sharma, S. The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer’s disease. Cell Biochem. Funct., 2022, 40(2), 106-117.
[http://dx.doi.org/10.1002/cbf.3680] [PMID: 34931308]
[75]
Zhi, J.; Zhai, S. Effects of piragliatin, a glucokinase activator, on fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus. J. Clin. Pharmacol., 2016, 56(2), 231-238.
[http://dx.doi.org/10.1002/jcph.589] [PMID: 26183686]
[76]
Klein, K.R.; Freeman, J.L.R.; Dunn, I.; Dvergsten, C.; Kirkman, M.S.; Buse, J.B.; Valcarce, C.; Buse, J.B.; Klein, K.R.; Kirkman, M.S.; Bergamo, K.A.; Harris, E.H.; Dostou, J.M.; Young, L.A.; Machineni, S.; Kass, A.M.; Diner, J.C.; Dezube, M.; Purrington, V.C.; Uehling, J.M. The simplicit1 study: A randomized, double-blind, placebo-controlled phase 1b/2 adaptive study of TTP399, a hepatoselective glu-cokinase activator, for adjunctive treatment of type 1 diabetes. Diabetes Care, 2021, 44(4), 960-968.
[http://dx.doi.org/10.2337/dc20-2684] [PMID: 33622669]
[77]
Amin, N.B.; Aggarwal, N.; Pall, D.; Paragh, G.; Denney, W.S.; Le, V.; Riggs, M.; Calle, R.A. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes. Metab., 2015, 17(8), 751-759.
[http://dx.doi.org/10.1111/dom.12474] [PMID: 25885172]
[78]
Denney, W.S.; Denham, D.S.; Riggs, M.R.; Amin, N.B. Glycemic effect and safety of a systemic, partial glucokinase activator, PF-04937319, in patients with type 2 diabetes mellitus inadequately controlled on metformin-A randomized, crossover, active-controlled study. Clin. Pharmacol. Drug Dev., 2016, 5(6), 517-527.
[http://dx.doi.org/10.1002/cpdd.261] [PMID: 27870481]
[79]
Zhu, D.; Gan, S.; Liu, Y.; Ma, J.; Dong, X.; Song, W.; Zeng, J.; Wang, G.; Zhao, W.; Zhang, Q.; Li, Y.; Fang, H.; Lv, X.; Shi, Y.; Tian, H.; Ji, L.; Gao, X.; Zhang, L.; Bao, Y.; Lei, M.; Li, L.; Zeng, L.; Li, X.; Hou, X.; Zhao, Y.; Hu, T.; Ge, X.; Zhao, G.; Li, Y.; Zhang, Y.; Chen, L. Dorzagliatin monotherapy in chinese patients with type 2 diabetes: A dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Diabetes Endocrinol., 2018, 6(8), 627-636.
[http://dx.doi.org/10.1016/S2213-8587(18)30105-0] [PMID: 29735394]
[80]
Katz, L.; Manamley, N.; Snyder, W.J.; Dodds, M.; Agafonova, N.; Sierra-Johnson, J.; Cruz, M.; Kaur, P.; Mudaliar, S.; Raskin, P.; Kewalramani, R.; Pellacani, A. AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes. Diabetes Obes. Metab., 2016, 18(2), 191-195.
[http://dx.doi.org/10.1111/dom.12586] [PMID: 26434934]
[81]
Wilding, J.P.H.; Leonsson-Zachrisson, M.; Wessman, C.; Johnsson, E. Dose-ranging study with the glucokinase activator AZD1656 in patients with type 2 diabetes mellitus on metformin. Diabetes Obes. Metab., 2013, 15(8), 750-759.
[http://dx.doi.org/10.1111/dom.12088] [PMID: 23464532]
[82]
Kiyosue, A.; Hayashi, N.; Komori, H.; Leonsson-Zachrisson, M.; Johnsson, E. Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus. Diabetes Obes. Metab., 2013, 15(10), 923-930.
[http://dx.doi.org/10.1111/dom.12100] [PMID: 23522182]

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