Ion Channels as Therapeutic Targets for Type 1 Diabetes Mellitus

Author(s): Chandrabose Selvaraj*, Gurudeeban Selvaraj, Satyavani Kaliamurthi, William C. Cho, Dong-Qing Wei*, Sanjeev Kumar Singh*

Journal Name: Current Drug Targets

Volume 21 , Issue 2 , 2020


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Graphical Abstract:


Abstract:

Ion channels are integral proteins expressed in almost all living cells and are involved in muscle contraction and nutrient transport. They play a critical role in the normal functioning of the excitable tissues of the nervous system and regulate the action potential and contraction events. Dysfunction of genes encodes ion channel proteins, which disrupt the channel function and lead to a number of diseases, among which is type 1 diabetes mellitus (T1DM). Therefore, understanding the complex mechanism of ion channel receptors is necessary to facilitate the diagnosis and management of treatment. In this review, we summarize the mechanism of important ion channels and their potential role in the regulation of insulin secretion along with the limitations of ion channels as therapeutic targets. Furthermore, we discuss the recent investigations of the mechanism regulating the ion channels in pancreatic beta cells, which suggest that ion channels are active participants in the regulation of insulin secretion.

Keywords: Ion channels, channelopathies, autoimmune disorder, T1DM, SUR1, pancreatic beta cells.

[1]
Samaras V, Rafailidis PI, Mourtzoukou EG, Peppas G, Falagas ME. Chronic bacterial and parasitic infections and cancer: a review. J Infect Dev Ctries 2010; 4: 267-81.
[http://dx.doi.org/10.3855/jidc.819]
[2]
Zhao M, Wei DQ. Rare diseases: Drug discovery and informatics resource. Interdiscip Sci Comput Life Sci 2018; 10: 195-204.
[http://dx.doi.org/10.1007/s12539-017-0270-3]
[3]
Selvaraj G, Selvaraj C, Wei DQ. Computational advances in chronic diseases diagnostics and therapy – II. Curr Drug Targets 2020; 21: 1-2.
[4]
Attali B, Gao ZB. Ion channels research in the post-genomic era. Acta Pharmacol Sin 2016; 37: 1-3.
[http://dx.doi.org/10.1038/aps.2015.144]
[5]
Kullmann DM, Hanna MG. Neurological disorders caused by inherited ion-channel mutations. Lancet Neurol 2002; 1: 157-66.
[http://dx.doi.org/10.1016/S1474-4422(02)00071-6]
[6]
Rubaiy HN. The therapeutic agents that target ATP-sensitive potassium channels. Acta Pharm 2016; 66: 23-34.
[http://dx.doi.org/10.1515/acph-2016-0006]
[7]
Grisshammer R, Tate CG. Overexpression of integral membrane proteins for structural studies. Q Rev Biophys 1995; 28: 315-422.
[http://dx.doi.org/10.1017/S0033583500003504]
[8]
Hermans MP. Diabetes and the endothelium. Acta Clin Belg 2007; 62: 97-101.
[http://dx.doi.org/10.1179/acb.2007.017]
[9]
Singh PP, Mahadi F, Roy A, Sharma P. Reactive oxygen species, reactive nitrogen species and antioxidants in etiopathogenesis of diabetes mellitus type-2. Indian J Clin Biochem 2009; 24: 324-42.
[http://dx.doi.org/10.1007/s12291-009-0062-6]
[10]
Matsumoto T, Yoshiyama S, Wakabayashi K, Koboyashi T, Kamata K. Effect of chronic insulin on cromakalim-induced relaxation in established streptozotocin-diabetic rat basilar artery. Eur J Pharmacol 2004; 504: 129-37.
[http://dx.doi.org/10.1016/j.ejphar.2004.09.031]
[11]
Liu Y, Gutterman DD. The coronary circulation in diabetes: Influence of reactive oxygen species on K+ channel-mediated vasodilation. Vascul Pharmacol 2002; 8: 43-9.
[http://dx.doi.org/10.1016/S1537-1891(02)00125-8]
[12]
Dean PM, Matthews EK. Electrical activity in pancreatic islet cells. Nature 1968; 219: 389-90.
[http://dx.doi.org/10.1038/219389a0]
[13]
Dukes ID, Philipson LH. K channels: generating excitement in pancreatic β-cells. Diabetes 1996; 1996(45): 845-53.
[http://dx.doi.org/10.2337/diab.45.7.845]
[14]
Hiriart M, Velasco M, Larqué Velázquez CA, Díaz García C. Metabolic Syndrome and Ionic Channels in Pancreatic Beta Cells -. Vitam Horm 2014; 95: 87-114.
[http://dx.doi.org/10.1016/B978-0-12-800174-5.00004-1]
[15]
Buckingham SD, Kidd JF, Law RJ, Franks CJ, Sattelle DB. Structure and function of two-pore-domain K? channels: contributions from genetic model organisms. Trends Pharmacol Sci 2005; 26: 361-7.
[http://dx.doi.org/10.1016/j.tips.2005.05.003]
[16]
Tian C, Zhu R, Zhu L, Qiu T, Cao Z, Kang T. Potassium channels: structures, diseases, and modulators. Chem Biol Drug Des 2014; 83: 1-26.
[http://dx.doi.org/10.1111/cbdd.12237]
[17]
Schreiber M, Wei A, Yuan A, Gaut J, Saito M, Salkoff L. Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J Biol Chem 1998; 273: 3509-16.
[http://dx.doi.org/10.1074/jbc.273.6.3509]
[18]
Meera P, Wallner M, Song M, Toro L. Large conductance voltage and calcium-dependent K+ channel, a distinct member of voltage dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc Natl Acad Sci USA 1997; 94: 14066-71.
[http://dx.doi.org/10.1073/pnas.94.25.14066]
[19]
Bezanilla F. The voltage sensor in voltage-dependent ion channels. Physiol Rev 2000; 80: 555-92.
[http://dx.doi.org/10.1152/physrev.2000.80.2.555]
[20]
Sigworth FJ. Voltage gating of ion channels. Q Rev Biophys 1994; 27: 1-40.
[http://dx.doi.org/10.1017/S0033583500002894]
[21]
Wickman K, Clapham DE. Ion channel regulation by G proteins. Physiol Rev 1995; 75: 865-85.
[http://dx.doi.org/10.1152/physrev.1995.75.4.865]
[22]
Alexander SP, Kelly E, Marrion N, et al. The Concise Guide to Pharmacology 2013/14: Overview. Br J Pharmacol 2013; 170: 1449-867.
[http://dx.doi.org/10.1111/bph.12444]
[23]
Fridlyand LE, Jacobson DA, Philipson LH. Ion channels and regulation of insulin secretion in human β-cells: a computational systems analysis. Islets 2013; 5(1): 1-15.
[http://dx.doi.org/10.4161/isl.24166]
[24]
Shyng S, Nichols CG. Octameric stoichiometry of the KATP channel complex. J Gen Physiol 1997; 110: 655-64.
[http://dx.doi.org/10.1085/jgp.110.6.655]
[25]
Inagaki N, Gonoi T, Clement JPT, et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 1995; 270: 1166-70.
[http://dx.doi.org/10.1126/science.270.5239.1166]
[26]
Inagaki N, Tsuura Y, Namba N, et al. Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem 1995; 270: 5691-4.
[http://dx.doi.org/10.1074/jbc.270.11.5691]
[27]
Babenko AP, Gonzalez GC, Bryan J. Hetero-concatemeric KIR6.X4/SUR14 channels display distinct conductivities but uniform ATP inhibition. J Biol Chem 2000; 275: 31563-6.
[http://dx.doi.org/10.1074/jbc.C000553200]
[28]
Miki T, Nagashima K, Tashiro F, et al. Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci USA 1998; 95: 10402-6.
[http://dx.doi.org/10.1073/pnas.95.18.10402]
[29]
Pasyk EA, Kang Y, Huang X, Cui N, Sheu L, Gaisano HY. Syntaxin-1A binds the nucleotide-binding folds of sulphonylurea receptor 1 to regulate the KATP channel. J Biol Chem 2004; 279: 4234-40.
[http://dx.doi.org/10.1074/jbc.M309667200]
[30]
Cui N, Kang Y, He Y, et al. H3 domain of syntaxin 1A inhibits KATP channels by its actions on the sulfonylurea receptor 1 nucleotide-binding folds-1 and -2. J Biol Chem 2004; 279: 53259-65.
[http://dx.doi.org/10.1074/jbc.M410171200]
[31]
Kang Y, Leung YM, Manning-Fox JE, et al. Syntaxin-1A inhibits cardiac KATP channels by its actions on nucleotide binding folds 1 and 2 of sulfonylurea receptor 2A. J Biol Chem 2004; 279: 47125-31.
[http://dx.doi.org/10.1074/jbc.M404954200]
[32]
Ashcroft FM, Gribble FM. Correlating structure and function in ATPsensitive K channels. Trends Neurosci 1998; 21: 288-94.
[http://dx.doi.org/10.1016/S0166-2236(98)01225-9]
[33]
Yokoshiki H, Sunagawa M, Seki T, Sperelakis N. ATP-sensitive K channels in pancreatic, cardiac, and vascular smooth muscle cells. Am J Physiol 1998; 274: C25-37.
[http://dx.doi.org/10.1152/ajpcell.1998.274.1.C25]
[34]
Chen PC, Bruederle CE, Gaisano HY, Shyng SL. Syntaxin 1A regulates surface expression of beta-cell ATP-sensitive potassium channels. Am J Physiol Cell Physiol 2011; 300: C506-16.
[http://dx.doi.org/10.1152/ajpcell.00429.2010]
[35]
Ashcroft FM, Harrison DE, Ashcroft SJH. Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature 1984; 312: 446-8.
[http://dx.doi.org/10.1038/312446a0]
[36]
Koster JC, Marshall BA, Ensor N, Corbett JA, Nichols CG. Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell 2000; 100: 645-54.
[http://dx.doi.org/10.1016/S0092-8674(00)80701-1]
[37]
Dunne MJ, Cosgrove KE, Shepherd RM, Aynsley-Green A, Lindley KJ. Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev 2004; 84: 239-75.
[http://dx.doi.org/10.1152/physrev.00022.2003]
[38]
Gloyn AL, Pearson ER, Antcliff JF, et al. Activating mutations in the ATP-sensitive potassium channel subunit Kir6.2 gene are associated with permanent neonatal diabetes. N Engl J Med 2004; 350: 1838-49.
[http://dx.doi.org/10.1056/NEJMoa032922]
[39]
Gopel SO, Kanno T, Barg S, Weng XG, Gromada J, Rorsman P. Regulation of glucagon release in mouse alpha-cells by KATP channels and inactivation of TTX-sensitive Na+ channels. J Physiol 2000; 528: 509-20.
[http://dx.doi.org/10.1111/j.1469-7793.2000.00509.x]
[40]
Gopel SO, Kanno T, Barg S, Rorsman P. Patch-clamp characterization of somatostatin-secreting δ-cells in intact mouse pancreatic islets. J Physiol 2000; 528: 497-507.
[http://dx.doi.org/10.1111/j.1469-7793.2000.00497.x]
[41]
Wang R, Liu X, Hentges ST, et al. The regulation of glucose excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. Diabetes 2004; 53: 1959-65.
[http://dx.doi.org/10.2337/diabetes.53.8.1959]
[42]
Zingman LV, Hodgson DM, Bast PH, et al. Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci USA 2002; 99: 13278-83.
[http://dx.doi.org/10.1073/pnas.212315199]
[43]
Edghill EL, Gloyn AL, Gillespie KM, et al. Activating mutations in the KCNJ11 gene encoding the ATP-sensitive K+ channel subunit Kir6.2 are rare in clinically defined type 1 diabetes diagnosed before 2 years. Diabetes 2004; 53: 2998-3001.
[http://dx.doi.org/10.2337/diabetes.53.11.2998]
[44]
Gribble F, Ashcroft FM. New windows on the mechanism of action of potassium channel openers. Trends Pharmacol Sci 2000; 21: 439-45. [review].
[http://dx.doi.org/10.1016/S0165-6147(00)01563-7]
[45]
Henquin JC. Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia 2009; 52: 739-51.
[http://dx.doi.org/10.1007/s00125-009-1314-y]
[46]
Kukuljan M, Goncalves AA, Atwater I. Charybdotoxin-sensitive KCa channel is not involved in glucose-induced electrical activity in pancreatic beta-cells. J Membr Biol 1991; 119: 187-95.
[http://dx.doi.org/10.1007/BF01871418]
[47]
Gopel SO, Kanno T, Barg S, et al. Activation of Ca2-dependent K channels contributes to rhythmic firing of action potentials in mouse pancreatic beta cells. J Gen Physiol 1999; 114: 759-70.
[http://dx.doi.org/10.1085/jgp.114.6.759]
[48]
Rorsman P, Eliasson L, Renstrom E, Gromada J, Barg S, Gopel S. The cell physiology of biphasic insulin secretion. News Physiol Sci 2000; 15: 72-7.
[http://dx.doi.org/10.1152/physiologyonline.2000.15.2.72]
[49]
Smith PA, Bokvist K, Arkhammar P, Berggren PO, Rorsman P. Delayed rectifying and calcium-activated K channels and their significance for action potential repolarization in mouse pancreatic beta-cells. J Gen Physiol 1999; 95: 1041-59.
[http://dx.doi.org/10.1085/jgp.95.6.1041]
[50]
Smith PA, Bokvist K, Rorsman P. Demonstration of A-currents in pancreatic islet cells. Pflugers Arch 1989; 413: 441-3.
[http://dx.doi.org/10.1007/BF00584497]
[51]
Zunkler BJ, Trube G, Ohno-Shosaku T. Forskolin-induced block of delayed rectifying K channels in pancreatic beta-cells is not mediated by cAMP. Pflugers Arch 1988; 411: 613-9.
[http://dx.doi.org/10.1007/BF00580856]
[52]
Philipson LH, Rosenberg MP, Kuznetsov A, et al. Delayed rectifier K channel overexpression in transgenic islets and beta-cells associated with impaired glucose responsiveness. J Biol Chem 1994; 269: 27787-90.
[53]
Roe MW, Worley JF III, Mittal AA, et al. Expression and function of pancreatic beta-cell delayed rectifier K channels: role in stimulus-secretion coupling. J Biol Chem 1996; 271: 32241-6.
[http://dx.doi.org/10.1074/jbc.271.50.32241]
[54]
Eberhardson M, Tengholm A, Grapengiesser E. The role of plasma membrane K and Ca2 permeabilities for glucose induction of slow Ca2oscillations in pancreatic beta-cells. Biochim Biophys Acta 1996; 1283: 67-72.
[http://dx.doi.org/10.1016/0005-2736(96)00075-2]
[55]
MacDonald PE, Salapatek AM, Wheeler MB. Glucagon-like peptide-1 receptor activation antagonizes voltage-dependent repolarizing K currents in -cells: a possible glucose-dependent insulinotropic mechanism. Diabetes 2002; 51: S443-7.
[http://dx.doi.org/10.2337/diabetes.51.2007.S443]
[56]
Kanno T, Gopel SO, Rorsman P, Wakui M. Cellular function in multicellular system for hormone-secretion: electrophysiological aspect of studies on alpha-, beta- and delta-cells of the pancreatic islet. Neurosci Res 2002; 42: 79-90.
[http://dx.doi.org/10.1016/S0168-0102(01)00318-2]
[57]
Harmar AJ, Hills RA, Rosser EM, et al. Spedding MIUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res 2009; 37: D680-5.
[58]
Rorsman P. The pancreatic beta-cell as a fuel sensor: an electrophysiologist’s viewpoint. Diabetologia 1997; 40: 487-4985.
[http://dx.doi.org/10.1007/s001250050706]
[59]
Braun M, Ramracheya R, Bengtsson M, et al. Voltage-gated ion channels in human pancreatic beta-cells: electrophysiological characterization and role in insulin secretion. Diabetes 2008; 57: 1618-28.
[http://dx.doi.org/10.2337/db07-0991]
[60]
Long SB, Campbell EB, Mackinnon R. Crystal structure of a mammalian voltage-dependent Shaker family K+channel. Science 2005; 309: 897-903.
[http://dx.doi.org/10.1126/science.1116269]
[61]
Long SB, Campbell EB, Mackinnon R. Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 2005; 309: 903-8.
[http://dx.doi.org/10.1126/science.1116270]
[62]
Dworakowska B, Dołowy K. Ion channels-related diseases. Acta Biochim Pol 2000; 47: 685-703.
[63]
Bocksteins E. Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders. J Gen Physiol 2016; 147: 105-25.
[http://dx.doi.org/10.1085/jgp.201511507]
[64]
Bocksteins E, Snyders DJ. Electrically silent Kv subunits: their molecular and functional characteristics. Physiology (Bethesda) 2012; 27: 73-84.
[http://dx.doi.org/10.1152/physiol.00023.2011]
[65]
Pal S, Hartnett KA, Nerbonne JM, Levitan ES, Aizenman E. Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels. J Neurosci 2003; 23: 4798-802.
[http://dx.doi.org/10.1523/JNEUROSCI.23-12-04798.2003]
[66]
Dai XQ, Manning JE, Fox D, Chikvashvili M, Casimir G, Plummer C. The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function. Diabetologia 2012; 55: 1709-20.
[http://dx.doi.org/10.1007/s00125-012-2512-6]
[67]
Frazzini V, Guarnieri S, Bomba M, et al. Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer’s disease mouse model. Cell Death Dis 2016. 7e2100
[http://dx.doi.org/10.1038/cddis.2016.18]
[68]
Schwiening CJ. A brief historical perspective: Hodgkin and Huxley. J Physiol 2012; 590: 2571-5.
[http://dx.doi.org/10.1113/jphysiol.2012.230458]
[69]
Hille B. Ionic Channels of Excitable Membranes. 3rd ed. Sunderland, MA: Sinauer Associates Inc 2001.
[70]
Catterall WA. Voltage-gated sodium channels at 60: Structure, function and pathophysiology. J Physiol 2012; 590: 2577-89.
[http://dx.doi.org/10.1113/jphysiol.2011.224204]
[71]
Marban E, Yamagishi T, Tomaselli GF. Structure and function of voltage-gated sodium channel. J Physiol 1998; 508: 647-57.
[http://dx.doi.org/10.1111/j.1469-7793.1998.647bp.x]
[72]
Waxman SG. Painful Na-channelopathies: An expanding universe. Trends Mol Med 2013; 19: 406-9.
[http://dx.doi.org/10.1016/j.molmed.2013.04.003]
[73]
Zhang MM, Wilson MJ, Gajewiak J, et al. Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by μ-conotoxins. Br J Pharmacol 2013; 169: 102-14.
[http://dx.doi.org/10.1111/bph.12119]
[74]
Zhang Q, Chibalina MV, Bengtsson M, et al. Na+ current properties in islet α-and β-cells reflect cell-specific Scn3a and Scn9a expression. J Physiol 2014; 592: 4677-96.
[http://dx.doi.org/10.1113/jphysiol.2014.274209]
[75]
Zhang Q, Ramracheya R, Lahmann C, et al. Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes. Cell Metab 2013; 18: 871-82.
[http://dx.doi.org/10.1016/j.cmet.2013.10.014]
[76]
Nita II, Hershfinkel M, Kantor C, Rutter GA, Lewis EC, Sekler I. Pancreatic β-cell Na+ channels control global Ca2+ signaling and oxidative metabolism by inducing Na+ and Ca2+ responses that are propagated into mitochondria. FASEB J 2014; 28: 3301-12.
[http://dx.doi.org/10.1096/fj.13-248161]
[77]
Yang YHC, Vilin YY, Roberge M, Kurata HT, Johnson JD. Multiparameter Screening Reveals a Role for Na+ Channels in Cytokine-Induced β-Cell Death. Mol Endocrinol 2014; 28: 406-17.
[http://dx.doi.org/10.1210/me.2013-1257]
[78]
Verkman AS, Galietta LJ. Chloride channels as drug targets. Nat Rev Drug Discov 2009; 8: 153-71.
[http://dx.doi.org/10.1038/nrd2780]
[79]
Mazzone A, Cheryl EB, Peter RS, et al. Altered Expression of Ano1 Variants in Human Diabetic Gastroparesis. J Biol Chem 2011; 286: 13393-403.
[http://dx.doi.org/10.1074/jbc.M110.196089]
[80]
Hall AM, Throesch BT, Buckingham SC. Tau-dependent Kv4.2 depletion and dendritic hyperexcitability in a mouse model of Alzheimer’s disease. J Neurosci 2015; 35: 6221-30.
[http://dx.doi.org/10.1523/JNEUROSCI.2552-14.2015]
[81]
Verkman AS, Galietta LJ. Chloride channels as drug targets. Nat Rev Drug Discov 2009; 8: 153-71.
[http://dx.doi.org/10.1038/nrd2780]
[82]
Riordan JR, Rommens JM, Kerem BS, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989; 245: 1066-73.
[http://dx.doi.org/10.1126/science.2475911]
[83]
Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol 1992; 8: 67-113.
[http://dx.doi.org/10.1146/annurev.cb.08.110192.000435]
[84]
Arya H, Syed SB, Singh SS, et al. In silico investigations of chemical constituents of clerodendrum colebrookianum in the anti-hypertensive drug targets: ROCK, ACE, and PDE5. Interdiscip Sci Comput Life Sci 2018; 10: 792-804.
[http://dx.doi.org/10.1007/s12539-017-0243-6]
[85]
Hyde SC, Emsley P, Hartshorn MJ, et al. Structural model of ATP binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature 1990; 346: 362-5.
[http://dx.doi.org/10.1038/346362a0]
[86]
Rorsman P, Berggren P, Bokvist K, et al. Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. Nature 1989; 341: 233-6.
[http://dx.doi.org/10.1038/341233a0]
[87]
Feske S, Skolnik EY, Prakriya M. Ion channels and transporters in lymphocyte function and immunity. Nat Rev Immunol 2012; 12: 532-47.
[http://dx.doi.org/10.1038/nri3233]
[88]
Koch MC, Steinmeyer K, Lorenz C, et al. The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 1992; 257: 797-800.
[http://dx.doi.org/10.1126/science.1379744]
[89]
Matsumura Y, Uchida S, Kondo Y, Miyazaki H, Ko SB, Hayama A. Overt nephrogenic diabetes insipidus in mice lacking the CLCK1 chloride channel. Nat Genet 1999; 21: 95-8.
[http://dx.doi.org/10.1038/5036]
[90]
Cahalan MD, Chandy KG. The functional network of ion channels in T lymphocytes. Immunol Rev 2009; 231: 59-87.
[http://dx.doi.org/10.1111/j.1600-065X.2009.00816.x]
[91]
Eil R, Vodnala SK, Clever D, Klebanoff CA, Sukumar M, Pan JH. Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature 2016; 537: 539-43.
[http://dx.doi.org/10.1038/nature19364]
[92]
Wagstaff AJ, Goa KL. Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs 2002; 62: 1805-37.
[http://dx.doi.org/10.2165/00003495-200262120-00007]
[93]
Cahalan MD, Chandy KG. Ion channels in the immune system as targets for immunosuppression. Curr Opin Biotechnol 1997; 8: 749-56.
[http://dx.doi.org/10.1016/S0958-1669(97)80130-9]
[94]
Matko JK. + channels and T-cell synapses: the molecular background for efficient immunomodulation is shaping up. Trends Pharmacol Sci 2003; 24: 385-9.
[http://dx.doi.org/10.1016/S0165-6147(03)00198-6]
[95]
Nicolaou SA, Neumeier L, Peng Y, Devor DC, Conforti L. The Ca2+-activated K+ channel KCa3.1 compartmentalizes in the immunological synapse of human T lymphocytes. Am J Physiol Cell Physiol 2007; 292: C1431-9.
[http://dx.doi.org/10.1152/ajpcell.00376.2006]
[96]
Cahalan MD, Chandy KG. The functional network of ion channels in T lymphocytes. Immunol Rev 2009; 231: 59-87.
[http://dx.doi.org/10.1111/j.1600-065X.2009.00816.x]
[97]
Derler I, Schindl R, Fritsch R, Romanin C. Gating and permeation of Orai channels. Front Biosci 2012; 1: 1304-22.
[http://dx.doi.org/10.2741/3988]
[98]
Chang WC, Parekh AB. Close functional coupling between Ca2+ release-activatedCa2+ channels, arachidonic acid release, and leukotriene C4 secretion. J Biol Chem 2004; 279: 29994-9.
[http://dx.doi.org/10.1074/jbc.M403969200]
[99]
Badou A, Jha MK, Matza D, et al. Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function. Proc Natl Acad Sci USA 2006; 103: 15529-34.
[http://dx.doi.org/10.1073/pnas.0607262103]
[100]
Matza D, Badou A, Kobayashi KS, et al. A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation. Immunity 2008; 28: 64-74.
[http://dx.doi.org/10.1016/j.immuni.2007.11.020]
[101]
Matza D, Flavell RA. Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast. Immunol Rev 2009; 231: 257-64.
[http://dx.doi.org/10.1111/j.1600-065X.2009.00805.x]
[102]
Jha MK, Badou A, Meissner M, McRory JE, Freichel M, Flockerzi V. Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels. Nat Immunol 2009; 10: 1275-82.
[http://dx.doi.org/10.1038/ni.1793]
[103]
Matza D, Badou A, Jha MK, et al. Requirement for AHNAK1-mediated calcium signaling during T lymphocyte cytolysis. Proc Natl Acad Sci USA 2009; 106: 9785-90.
[http://dx.doi.org/10.1073/pnas.0902844106]
[104]
Baughman JM, Perocchi F, Girgis HS, et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 2011; 476: 341-5.
[http://dx.doi.org/10.1038/nature10234]
[105]
Liou J, Kim ML, Heo WD, et al. STIM is a Ca2+ sensor essential for Ca2+- store-depletion-triggered Ca2+ influx. Curr Biol 2005; 15: 1235-41.
[http://dx.doi.org/10.1016/j.cub.2005.05.055]
[106]
Feske S. Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol 2007; 7: 690-702.
[http://dx.doi.org/10.1038/nri2152]
[107]
Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245-52.
[http://dx.doi.org/10.1038/32588]
[108]
Johnston D, Narayanan R. Active dendrites: colorful wings of the mysterious butterflies. Trends Neurosci 2008; 31: 309-16.
[http://dx.doi.org/10.1016/j.tins.2008.03.004]
[109]
Cahalan MD, Wulff H, Chandy KG. Molecular properties and physiological roles of ion channels in the immune system. J Clin Immunol 2001; 21: 235-52.
[http://dx.doi.org/10.1023/A:1010958907271]
[110]
Connolly SF, Kusner DJ. The regulation of dendritic cell function by calcium-signaling and its inhibition by microbial pathogens. Immunol Res 2007; 39: 115-27.
[http://dx.doi.org/10.1007/s12026-007-0076-1]
[111]
Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767-811.
[http://dx.doi.org/10.1146/annurev.immunol.18.1.767]
[112]
Zhao Y, Huang J, Yuan X, et al. Toxins Targeting the Kv1.3 Channel: Potential Immunomodulators for Autoimmune Diseases. Toxins (Basel) 2015; 7: 1749-64.
[http://dx.doi.org/10.3390/toxins7051749]
[113]
Panyi G, Varga Z, Gaspar R. Ion channels and lymphocyte activation. Immunol Lett 2004; 92: 55-66.
[http://dx.doi.org/10.1016/j.imlet.2003.11.020]
[114]
Vicente R, Escalada A, Soler C, Grande M, Celada A, Tamkun MM. Pattern of Kv subunit expression in macrophages depends upon proliferation and the mode of activation. J Immunol 2005; 174: 4736-44.
[http://dx.doi.org/10.4049/jimmunol.174.8.4736]
[115]
Kis-Toth K, Hajdu P, Bacskai I, Szilagyi O, Papp F, Szanto A. Voltage-gated sodium channel Nav1.7 maintains the membrane potential and regulates the activation and chemokine-induced migration of a monocyte-derived dendritic cell subset. J Immunol 2011; 187: 1273-80.
[http://dx.doi.org/10.4049/jimmunol.1003345]
[116]
Zsiros E, Kis-Toth K, Hajdu P, et al. Developmental switch of the expression of ion channels in human dendritic cells. J Immunol 2009; 183: 4483-92.
[http://dx.doi.org/10.4049/jimmunol.0803003]
[117]
Mullen K, Rozycka M, Rus H, et al. Potassium channels Kv1.3 and Kv1.5 are expressed on blood-derived dendritic cells in the central nervous system. Ann Neurol 2006; 60: 118-27.
[http://dx.doi.org/10.1002/ana.20884]
[118]
Hille B. Ionic Channels of Excitable Membranes. Sunderland, MA: Sinauer 2001.
[119]
Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet JP. TRPM4 regulates calcium oscillations after T cell activation. Science 2004; 306: 1374-7.
[http://dx.doi.org/10.1126/science.1098845]
[120]
Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 2002; 109: 397-407.
[http://dx.doi.org/10.1016/S0092-8674(02)00719-5]
[121]
Cai X, Srivastava S, Sun Y, et al. Tripartite motif containing protein 27 negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II PI3K-C2β. Proc Natl Acad Sci USA 2011; 108: 20072-7.
[http://dx.doi.org/10.1073/pnas.1111233109]
[122]
Srivastava S, Di L, Zhdanova O, Li Z, et al. The class II phosphatidylinositol 3 kinase C2β is required for the activation of the K+ channel KCa3.1 and CD4 T-cells. Mol Biol Cell 2009; 20: 3783-91.
[http://dx.doi.org/10.1091/mbc.e09-05-0390]
[123]
Gerlach AC, Syme CA, Giltinan L, Adelman JP, Devor DC. ATP dependent activation of the intermediate conductance, Ca2+activated K+ channel, hIK1, is conferred by a C-terminal domain. J Biol Chem 2001; 276: 10963-70.
[http://dx.doi.org/10.1074/jbc.M007716200]
[124]
Blessia TF, Singh S, Vennila JJ. Unwinding the novel genes involved in the differentiation of embryonic stem cells into insulin-producing cells: A network-based approach. Interdiscip Sci Comput Life Sci 2017; 9: 88-95.
[125]
Porter JR, Barrett TG. Acquired non-type 1 diabetes in childhood: subtypes, diagnosis, and management. Arch Dis Child 2004; 89: 1138-44.
[http://dx.doi.org/10.1136/adc.2003.036608]
[126]
Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009; 360: 1646-54.
[http://dx.doi.org/10.1056/NEJMra0808284]
[127]
Erlich H, Valdes AM, Noble J, et al. Type 1 Diabetes Genetics Consortium. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 2008; 57: 1084-92.
[http://dx.doi.org/10.2337/db07-1331]
[128]
Schatz D, Krischer J, Horne G, et al. Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives. J Clin Invest 1994; 93: 2403-7.
[http://dx.doi.org/10.1172/JCI117247]
[129]
Imagawa A, Hanafusa T, Itoh N, et al. Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset type I (insulin-dependent) diabetes mellitus. Diabetologia 1999; 42: 574-8.
[http://dx.doi.org/10.1007/s001250051197]
[130]
Velasco M, Díaz-García CM, Larqué C, Hiriart M. Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells. Mol Pharmacol 2016; 90(3): 341-57.
[http://dx.doi.org/10.1124/mol.116.103861]
[131]
Ashcroft FM. From molecule to malady. Nature 2006; 440: 440-7.
[http://dx.doi.org/10.1038/nature04707]
[132]
Terlau H, Stuhmer W. Structure and function of voltage-gated ion channels. Naturwissenschaften 1998; 85: 437-44.
[http://dx.doi.org/10.1007/s001140050527]
[133]
Chang C, Ray A, Swaan P. In silico strategies for modeling membrane transporter function. Drug Discov Today 2005; 10: 663-71.
[http://dx.doi.org/10.1016/S1359-6446(05)03429-X]
[134]
Ashcroft F. Ion Channels and Disease. San Diego: Academic Press 2000; p. 48.
[135]
Herrington J, Zhou YP, Bugianesi RM, et al. Blockers of the delayed-rectifier potassium current in pancreatic beta cells enhances glucose-dependent insulin secretion. Diabetes 2006; 55: 1034-42.
[http://dx.doi.org/10.2337/diabetes.55.04.06.db05-0788]
[136]
Santos R, Ursu O, Gaulton A, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov 2017; 16: 19-34.
[http://dx.doi.org/10.1038/nrd.2016.230]
[137]
Selvaraj G, Kaliamurthi S, Thirugnasambandan R. Effect of Glycosin alkaloid from Rhizophora apiculata in non-insulin dependent diabetic rats and its mechanism of action: In vivo and in silico studies. Phytomedicine 2016; 23(6): 632-40.
[http://dx.doi.org/10.1016/j.phymed.2016.03.004]
[138]
Selvaraj G, Kaliamurthi S, Çakmak ZE, Çakmak T. In silico validation of microalgal metabolites against Diabetes mellitus. Diabetes mellitus 2017; 20(4): 301-7.
[http://dx.doi.org/10.14341/DM8212]
[139]
Selvaraj G, Kaliamurthi S, Thirugnasambandan R. Effect of dichloromethane fraction of Rhizophora mucronata on carbohydrate, lipid and protein metabolism in type 2 diabetic rats. Integr Obes Diabetes 2017; 3: 1-8.
[http://dx.doi.org/10.15761/IOD.1000182]
[140]
Gurudeeban S, Satyavani K, Ramanathan T, Balasubramanian T. Antidiabetic effect of a black mangrove species Aegiceras corniculatum in alloxan-induced diabetic rats. J Adv Pharm Technol Res 2012; 3(1): 52-6.
[141]
Henquin JC. Role of voltage- and Ca2+-dependent K+ channels in the control of glucose-induced electrical activity in pancreatic Bcells. Pflugers Arch 1990; 416: 568-72.
[http://dx.doi.org/10.1007/BF00382691]
[142]
Fernández-Ballester G, Fernández-Carvajal A, González-Ros JM, Ferrer-Montiel A. Ionic channels as targets for drug design: a review on computational methods. Pharmaceutics 2011; 3: 932-53.
[http://dx.doi.org/10.3390/pharmaceutics3040932]
[143]
Gurudeeban S, Satyavani K, Ramanathan T, Ravikumar P. Dipeptidyl peptidase IV inhibitors derived from a mangrove flora Rhizophora mucronata: An in silico approach. Bangladesh J Pharmacol 2012; 7(3): 203-10.
[http://dx.doi.org/10.3329/bjp.v7i3.11636]
[144]
Gurudeeban S, Satyavani K, Ramanathan T. Alpha-glucosidase inhibitory effect and enzyme kinetics of coastal medicinal plants. Bangladesh J Pharmacol 2012; 7(3): 186-91.
[http://dx.doi.org/10.3329/bjp.v7i3.11499]
[145]
Selvaraj G, Kaliamurthi S, Cakmak ZE, Cakmak T. Computational screening of dipeptidyl peptidase IV inhibitors from micoroalgal metabolites by pharmacophore modeling and molecular docking. Phycol Res 2016; 64(4): 291-9.
[http://dx.doi.org/10.1111/pre.12141]
[146]
Selvaraj C, Singh SK. Computational and Experimental Binding Mechanism ofDNA-drug Interactions. Curr Pharm Des 2018; 24(32): 3739-57.
[http://dx.doi.org/10.2174/1381612824666181106101448]
[147]
Bucher D, Rothlisberger U. Molecular simulations of ion channels: a quantum chemist’s perspective. J Gen Physiol 2010; 135: 549-54.
[http://dx.doi.org/10.1085/jgp.201010404]
[148]
Amarouch MY, Kasimova MA, Tarek M, Abriel H. Functional interaction between S1 and S4 segments in voltage-gated sodium channels revealed by human channelopathies. Channels (Austin) 2014; 8: 414-20.
[http://dx.doi.org/10.4161/19336950.2014.958922]
[149]
Heitz F, Van Mau N. Protein structural changes induced by their uptake atinterfaces. Biochim Biophys Acta 2002; 1597(1): 1-11.
[http://dx.doi.org/10.1016/S0167-4838(02)00273-X]
[150]
Selvaraj C, Sakkiah S, Tong W, Hong H. Molecular dynamics simulations and applications in computational toxicology and nanotoxicology. Food Chem Toxicol 2018; 112: 495-506.
[http://dx.doi.org/10.1016/j.fct.2017.08.028]
[151]
McRobb FM, Capuano B, Crosby IT, Chalmers DK, Yuriev E. Homology modeling and docking evaluation of aminergic G protein-coupled receptors. J Chem Inf Model 2010; 50: 626-37.
[http://dx.doi.org/10.1021/ci900444q]
[152]
Pedretti A, Marconi C, Bettinelli I, Vistoli G. Comparative modeling of the quaternary structure for the human TRPM8 channel and analysis of its binding features. Biochim Biophys Acta 2009; 1788: 973-82.
[http://dx.doi.org/10.1016/j.bbamem.2009.02.007]
[153]
Selvaraj C, Krishnasamy G, Jagtap SS, et al. Structural insights into the binding mode of D-sorbitol with sorbitoldehydrogenase using QM-polarized ligand docking and molecular dynamics simulations. Biochem Eng J 2016; 114: 244-56.
[http://dx.doi.org/10.1016/j.bej.2016.07.008]
[154]
Mansouri K, Abdelaziz A, Rybacka A, et al. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project. Environ Health Perspect 2016; 124: 1023-33.
[http://dx.doi.org/10.1289/ehp.1510267]
[155]
Sakkiah S, Selvaraj C, Gong P, Zhang C, Tong W, Hong H. Development of estrogen receptor beta binding prediction model using large sets of chemicals. Oncotarget 2017; 8(54): 92989-3000.
[http://dx.doi.org/10.18632/oncotarget.21723]
[156]
Muralidharan AR, Selvaraj C, Singh SK, Sheu JR, Thomas PA, Geraldine P. Structure-Based Virtual Screening and Biological Evaluation of a Calpain Inhibitor for Prevention of Selenite- Induced Cataractogenesis in an in VitroSystem. J Chem Inf Model 2015; 55(8): 1686-97.
[http://dx.doi.org/10.1021/acs.jcim.5b00092]
[157]
Cheng MH, Cascio M, Coalson RD. Homology modeling and molecular dynamics simulations of the alpha1 glycine receptor reveals different states of the channel. Proteins 2007; 68: 581-93.
[http://dx.doi.org/10.1002/prot.21435]
[158]
MacCoss M, Baillie TA. Organic chemistry in drug discovery. Science 2004; 303: 1810-3.
[http://dx.doi.org/10.1126/science.1096800]
[159]
Stolc S. Comparison of effects of selected local anesthetics on sodium and potassium channels in mammalian neuron. Gen Physiol Biophys 1988; 7: 177-89.
[160]
Sun S, Cohen CJ, Dehnhardt CM. Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since 2010. Pharm Pat Anal 2014; 3: 509-21.
[http://dx.doi.org/10.4155/ppa.14.39]
[161]
Jensen TS. Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain 2002; 6: 61-8.
[http://dx.doi.org/10.1053/eujp.2001.0324]
[162]
Milne JR, Hellestrand KJ, Bexton RS, Burnett PJ. Class 1 antiarrhythmic drugs--characteristic electrocardiographic differences when assessed by atrial and ventricular pacing. Eur Heart J 1984; 5: 99-107.
[http://dx.doi.org/10.1093/oxfordjournals.eurheartj.a061633]
[163]
Grant AO, Dietz MA, Gilliam FR, Starmer CF. Blockade of cardiac sodium channels by lidocaine. Single-channel analysis. Circ Res 1989; 65: 1247-62.
[http://dx.doi.org/10.1161/01.RES.65.5.1247]
[164]
Starmer CF, Nesterenko VV, Undrovinas AI, Grant AO, Rosenshtraukh LV. Lidocaineblockade of continuously and transiently accessible sites in cardiac sodium channels. J Mol Cell Cardiol 1991; 23: 73-83.
[http://dx.doi.org/10.1016/0022-2828(91) 90026-I]
[165]
Razavi M. Safe and effective pharmacologic management of arrhythmias. Tex Heart Inst J 2005; 32: 209-11.
[166]
Edrich T, Wang SY, Wang GK. State-dependent block of human cardiac hNav1.5 sodium channels by propafenone. J Membr Biol 2005; 207: 35-43.
[http://dx.doi.org/10.1007/s00232-005-0801-4]
[167]
Frank GB. A pharmacological explanation of the use-dependency of the verapamil (and D-600) block of slow calcium channels. J Pharmacol Exp Ther 1986; 236: 505-11.
[168]
Bagshaw SM, Galbraith PD, Mitchell LB, Sauve R, Exner DV. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a meta-analysis. Ann Thorac Surg 2006; 82: 1927-37.
[http://dx.doi.org/10.1016/j.athoracsur.2006.06.032]
[169]
Van Herendael H, Dorian P. Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia. Vasc Health Risk Manag 2010; 6: 465-72.
[170]
Katz AM, Hager WD, Messineo FC. Calcium Channel Blockers. Am J Med 1985; 77(Suppl. 2B): 2-10.
[http://dx.doi.org/10.1016/S0002-9343(84)80078-9]
[171]
Yousef WH, Omar AH, Morsy MD, Abd El-Wahed MM, Chanayem NM. The mechanism of action of calcium channel blockers in the treatment of diabetic nephropathy. Int J Diabetes Metab 2005; 13: 75-82.
[http://dx.doi.org/10.1159/000497574]
[172]
Robertson RM, Robertson D. Drugs used for the treatment of Myocardial Ischaemia In: Hardman JG, Limbird LE, Eds. Goodman and Gillman’s. USA:. The pharmacological Basis of Therapeutics, McGrawv-Hill 1996; pp. P767-79.
[173]
Wei DQ, Selvaraj G, Kaushik AC. Computational Perspective on the Current State of the Methods and New Challenges in Cancer Drug Discovery. Curr Pharm Des 2018; 24(32): 3725-6.
[http://dx.doi.org/10.2174/138161282432190109105339]
[174]
Sindrup SH, Otto M, Finnerup FB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol 2005; 96: 399-409.
[http://dx.doi.org/10.1111/j.1742-7843.2005.pto _96696601.x]
[175]
Hannon HE, Atchison WD. Omega-Conotoxins as experimental tools and therapeutic in pain management. Mar Drugs 2013; 11: 680-99.
[http://dx.doi.org/10.3390/md11030680]
[176]
Bode BW, Garg SK. The emerging role of adjunctive noninsulin antihyperglycemic therapy in the management of Type 1 Diabetes. Endocr Pract 2016; 22: 220-30.
[http://dx.doi.org/10.4158/EP15869.RA]
[177]
Anderberg RH, Richard JE, Eerola K, et al. Glucagon-Like Peptide-1 and its Analogues Act in the Dorsal Raphe and ModulateCentral Serotonin to Reduce Appetite and Body Weight. Diabetes 2017; 66(4): 1062-73.
[178]
Beeton C, Wulff H, Standifer NE, et al. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci USA 2006; 103: 17414-9.
[http://dx.doi.org/10.1073/pnas.0605136103]
[179]
Livingstone R, Boyle JG, Petrie JR. REMOVAL Study Team. A new perspective on metformin therapy in type 1 diabetes. Diabetologia 2017; 60: 1594-600.
[http://dx.doi.org/10.1007/s00125-017-4364-6]
[180]
Standards of medical care in diabetes 2017. Diabetes Care 2017; 40(Suppl. 1): S1-S35.
[181]
Solini A. Role of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus. Acta Diabetol 2016; 53: 863-70.
[http://dx.doi.org/10.1007/s00592-016-0856-y]
[182]
Li YH, Li XX, Hong JJ, et al. Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs. Brief Bioinform 2019.
[http://dx.doi.org/10.1093/bib/bby130]
[183]
Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol 2017; 5: 864-76.
[http://dx.doi.org/10.1016/S2213-8587(17)30308-X]
[184]
Herrington J, Zhou YP, Bugianesi RM, et al. Blockers of the delayed-rectifier potassium current in pancreatic β-cells enhance glucose-dependent insulin secretion. Diabetes 2006; 55: 1034-42.
[http://dx.doi.org/10.2337/diabetes.55.04.06.db05-0788]
[185]
Rosengren A, Jing X, Eliasson L, Renström E. Why Treatment Fails in Type 2 Diabetes. PLoS Med 2008. 5e215
[http://dx.doi.org/10.1371/journal.pmed.0050215]
[186]
Ahn HS, Kim SE, Jang HJ, et al. Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone. Naunyn Schmiedebergs Arch Pharmacol 2007; 374: 305-9.
[http://dx.doi.org/10.1007/s00210-006-0118-6]
[187]
Choi JS, Hahn SJ, Rhie DJ, Yoon SH, Jo YH, Kim MS. Mechanism of fluoxetine block of cloned voltage-activated potassium channel Kv1.3. J Pharmacol Exp Ther 1999; 291: 1-6.
[188]
Larsson O, Ammälä C, Bokvist K, Fredholm B, Rorsman P. Stimulation of the KATP channel by ADP and diazoxide requires nucleotide hydrolysis in mouse pancreatic beta-cells. J Physiol 1993; 463: 349-65.
[http://dx.doi.org/10.1113/jphysiol.1993.sp019598]
[189]
Sturgess NC, Ashford ML, Cook DL, Hales CN. The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet 1985; ii: 474-5.
[http://dx.doi.org/10.1016/S0140-6736(85)90403-9]
[190]
Landgraf R. Meglitinide analogues in the treatment of type 2 diabetes mellitus. Drugs Aging 2000; 17: 411-25.
[http://dx.doi.org/10.2165/00002512-200017050-00007]
[191]
Barrett R, Cavalla D, Coates IH, et al. Oxford, in Trends Med. Chem. ’90, Proc.Int Symp Med Chem. S Sarel, R Mechoulam, and I Agranat. Blackwell, Oxford 1992; p. 107.
[192]
Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A, Folli F. The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci 2013; 9(5): 936-43.
[http://dx.doi.org/10.5114/aoms.2013.34991]


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