{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:46:10Z","timestamp":1791474370325,"version":"4.3.4"},"reference-count":113,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T00:00:00Z","timestamp":1712361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005739","name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["DGAPA-PAPIIT IA207723"],"award-info":[{"award-number":["DGAPA-PAPIIT IA207723"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ionic channels are present in eucaryotic plasma and intracellular membranes. They coordinate and control several functions. Potassium channels belong to the most diverse family of ionic channels that includes ATP-dependent potassium (KATP) channels in the potassium rectifier channel subfamily. These channels were initially described in heart muscle and then in other tissues such as pancreatic, skeletal muscle, brain, and vascular and non-vascular smooth muscle tissues. In pancreatic beta cells, KATP channels are primarily responsible for maintaining the membrane potential and for depolarization-mediated insulin release, and their decreased density and activity may be related to insulin resistance. KATP channels\u2019 relationship with insulin resistance is beginning to be explored in extra-pancreatic beta tissues like the skeletal muscle, where KATP channels are involved in insulin-dependent glucose recapture and their activation may lead to insulin resistance. In adipose tissues, KATP channels containing Kir6.2 protein subunits could be related to the increase in free fatty acids and insulin resistance; therefore, pathological processes that promote prolonged adipocyte KATP channel inhibition might lead to obesity due to insulin resistance. In the central nervous system, KATP channel activation can regulate peripheric glycemia and lead to brain insulin resistance, an early peripheral alteration that can lead to the development of pathologies such as obesity and Type 2 Diabetes Mellitus (T2DM). In this review, we aim to discuss the characteristics of KATP channels, their relationship with clinical disorders, and their mechanisms and potential associations with peripheral and central insulin resistance.<\/jats:p>","DOI":"10.3390\/ijms25074079","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T09:31:23Z","timestamp":1712568683000},"page":"4079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Exploring the Pathophysiology of ATP-Dependent Potassium Channels in Insulin Resistance"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-181X","authenticated-orcid":false,"given":"Nidia Samara","family":"Rodr\u00edguez-Rivera","sequence":"first","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda y Bioqu\u00edmica Cl\u00ednica, Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Barrera-Oviedo","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda y Bioqu\u00edmica Cl\u00ednica, Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-3-319-56895-9_3","article-title":"Cell Membrane Transport Mechanisms: Ion Channels and Electrical Properties of Cell Membranes","volume":"227","author":"Kulbacka","year":"2017","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/HCO.0b013e328352429d","article-title":"Genetics of Ion-Channel Disorders","volume":"27","author":"Cerrone","year":"2012","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1107\/S2059798320003599","article-title":"Ion Permeation in Potassium Ion Channels","volume":"76","author":"Coates","year":"2020","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1007\/s00018-015-1948-5","article-title":"Structure of Potassium Channels","volume":"72","author":"Kuang","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/nrn1992","article-title":"High-Conductance Potassium Channels of the SLO Family","volume":"7","author":"Salkoff","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nrn1516","article-title":"Ca2+-Activated K+ Channels: Molecular Determinants and Function of the SK Family","volume":"5","author":"Stocker","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cbdd.12237","article-title":"Potassium Channels: Structures, Diseases, and Modulators","volume":"83","author":"Tian","year":"2014","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.hrthm.2004.05.002","article-title":"T Wave Morphology Analysis Distinguishes between KvLQT1 and HERG Mutations in Long QT Syndrome","volume":"1","author":"Kanters","year":"2004","journal-title":"Heart Rhythm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00160","DOI":"10.1002\/phy2.160","article-title":"Identification of Compound Heterozygous KCNJ1 Mutations (Encoding ROMK) in a Kindred with Bartter\u2019s Syndrome and a Functional Analysis of Their Pathogenicity","volume":"1","author":"Srivastava","year":"2013","journal-title":"Physiol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1113\/jphysiol.1984.sp015088","article-title":"Conductance Properties of Single Inwardly Rectifying Potassium Channels in Ventricular Cells from Guinea-Pig Heart","volume":"347","author":"Sakmann","year":"1984","journal-title":"J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0896-6273(00)80124-5","article-title":"A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K+ Channels","volume":"16","author":"Inagaki","year":"1996","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jsb.2009.11.005","article-title":"Quaternary Structure of KATP Channel SUR2A Nucleotide Binding Domains Resolved by Synchrotron Radiation X-Ray Scattering","volume":"169","author":"Park","year":"2010","journal-title":"J. Struct. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1126\/science.7716547","article-title":"Cloning of the Beta Cell High-Affinity Sulfonylurea Receptor: A Regulator of Insulin Secretion","volume":"268","author":"Nichols","year":"1995","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.2337\/diab.45.10.1439","article-title":"Cloning, Tissue Expression, and Chromosomal Localization of SUR2, the Putative Drug-Binding Subunit of Cardiac, Skeletal Muscle, and Vascular KATP Channels","volume":"45","author":"Chutkow","year":"1996","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"H33","DOI":"10.1152\/ajpheart.01088.2010","article-title":"Differential Roles for SUR Subunits in KATP Channel Membrane Targeting and Regulation","volume":"300","author":"Hund","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.2337\/diabetes.54.5.1592","article-title":"Single Nucleotide Polymorphisms in K(ATP) Channels: Muscular Impact on Type 2 Diabetes","volume":"54","author":"Li","year":"2005","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/0014-5793(95)01369-5","article-title":"Cloning and Functional Expression of the CDNA Encoding a Novel ATP-Sensitive Potassium Channel Subunit Expressed in Pancreatic Beta-Cells, Brain, Heart and Skeletal Muscle","volume":"377","author":"Sakura","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s100380200018","article-title":"Identification of 779 Genetic Variations in Eight Genes Encoding Members of the ATP-Binding Cassette, Subfamily C (ABCC\/MRP\/CFTR)","volume":"47","author":"Saito","year":"2002","journal-title":"J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"H1439","DOI":"10.1152\/ajpheart.00972.2012","article-title":"KIR 6.2 Is Not the Mitochondrial KATP Channel, but Is Required for Cardioprotection by Ischemic Preconditioning","volume":"304","author":"Wojtovich","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1152\/physrev.00021.2009","article-title":"Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles","volume":"90","author":"Hibino","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1046\/j.1471-4159.1996.67051982.x","article-title":"Colocalization of Glucagon-like Peptide-1 (GLP-1) Receptors, Glucose Transporter GLUT-2, and Glucokinase MRNAs in Rat Hypothalamic Cells: Evidence for a Role of GLP-1 Receptor Agonists as an Inhibitory Signal for Food and Water Intake","volume":"67","author":"Navarro","year":"1996","journal-title":"J. Neurochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/humu.20292","article-title":"Mutations in the Genes Encoding the Pancreatic Beta-Cell KATP Channel Subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in Diabetes Mellitus and Hyperinsulinism","volume":"27","author":"Gloyn","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1085\/jgp.95.6.1041","article-title":"Delayed Rectifying and Calcium-Activated K+ Channels and Their Significance for Action Potential Repolarization in Mouse Pancreatic Beta-Cells","volume":"95","author":"Smith","year":"1990","journal-title":"J. Gen. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1007\/s00125-003-1159-8","article-title":"Voltage-Dependent K+ Channels in Pancreatic Beta Cells: Role, Regulation and Potential as Therapeutic Targets","volume":"46","author":"MacDonald","year":"2003","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"845","DOI":"10.2337\/diab.45.7.845","article-title":"K+ Channels: Generating Excitement in Pancreatic Beta-Cells","volume":"45","author":"Dukes","year":"1996","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/BF00374906","article-title":"Bursting Electrical Activity in Pancreatic Beta-Cells: Evidence That the Channel Underlying the Burst Is Sensitive to Ca2+ Influx through L-Type Ca2+ Channels","volume":"424","author":"Barbosa","year":"1993","journal-title":"Pflugers Arch."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"758","DOI":"10.2337\/diabetes.47.5.758","article-title":"Glucose Activates Both K(ATP) Channel-Dependent and K(ATP) Channel-Independent Signaling Pathways in Human Islets","volume":"47","author":"Straub","year":"1998","journal-title":"Diabetes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1210\/endo.140.5.6729","article-title":"Glucose Regulation of Insulin Secretion Independent of the Opening or Closure of Adenosine Triphosphate-Sensitive K+ Channels in Beta Cells","volume":"140","author":"Sato","year":"1999","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/dmrr.329","article-title":"Glucose-Stimulated Signaling Pathways in Biphasic Insulin Secretion","volume":"18","author":"Straub","year":"2002","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_30","first-page":"101","article-title":"Molecular Biology of Adenosine Triphosphate-Sensitive Potassium Channels","volume":"20","author":"Bryan","year":"1999","journal-title":"Endocr. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12162","DOI":"10.1073\/pnas.96.21.12162","article-title":"Pharmacological Plasticity of Cardiac ATP-Sensitive Potassium Channels toward Diazoxide Revealed by ADP","volume":"96","author":"Moreau","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.2337\/diabetes.47.9.1412","article-title":"Tissue Specificity of Sulfonylureas: Studies on Cloned Cardiac and Beta-Cell K(ATP) Channels","volume":"47","author":"Gribble","year":"1998","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/cphy.c170048","article-title":"ATP-Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles","volume":"8","author":"Tinker","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1748-1716.2012.02481.x","article-title":"Potassium Channel Activators Differentially Modulate the Effect of Sodium Channel Blockade on Cardiac Conduction","volume":"207","author":"Veeraraghavan","year":"2013","journal-title":"Acta Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/01.RES.78.1.1","article-title":"Inward Rectification and Implications for Cardiac Excitability","volume":"78","author":"Nichols","year":"1996","journal-title":"Circ. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/370456a0","article-title":"Cloning and Functional Expression of a Rat Heart KATP Channel","volume":"370","author":"Ashford","year":"1994","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/312446a0","article-title":"Glucose Induces Closure of Single Potassium Channels in Isolated Rat Pancreatic Beta-Cells","volume":"312","author":"Ashcroft","year":"1984","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26383","DOI":"10.1074\/jbc.273.41.26383","article-title":"Mechanism of Cloned ATP-Sensitive Potassium Channel Activation by Oleoyl-CoA","volume":"273","author":"Gribble","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1113\/jphysiol.2003.059105","article-title":"Mapping the Architecture of the ATP-Binding Site of the KATP Channel Subunit Kir6.2","volume":"557","author":"Dabrowski","year":"2004","journal-title":"J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22983","DOI":"10.1074\/jbc.272.37.22983","article-title":"MgADP Antagonism to Mg2+-Independent ATP Binding of the Sulfonylurea Receptor SUR1","volume":"272","author":"Ueda","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s004240050332","article-title":"A Calcium-Dependent Chloride Current in Insulin-Secreting Beta TC-3 Cells","volume":"433","author":"Kozak","year":"1997","journal-title":"Pflugers Arch."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/BF01868728","article-title":"Inactivation Kinetics and Pharmacology Distinguish Two Calcium Currents in Mouse Pancreatic B-Cells","volume":"119","author":"Hopkins","year":"1991","journal-title":"J. Membr. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/311271a0","article-title":"Intracellular ATP Directly Blocks K+ Channels in Pancreatic B-Cells","volume":"311","author":"Cook","year":"1984","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF01872823","article-title":"Effects of ADP upon the ATP-Sensitive K+ Channel in Rat Ventricular Myocytes","volume":"101","author":"Findlay","year":"1988","journal-title":"J. Membr. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/BF02191896","article-title":"Functional Linkage of the Cardiac ATP-Sensitive K+ Channel to the Actin Cytoskeleton","volume":"431","author":"Furukawa","year":"1996","journal-title":"Pflugers Arch."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1126\/science.273.5277.956","article-title":"Regulation of Cardiac Na+,Ca2+ Exchange and KATP Potassium Channels by PIP2","volume":"273","author":"Hilgemann","year":"1996","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5388","DOI":"10.1074\/jbc.272.9.5388","article-title":"Anionic Phospholipids Activate ATP-Sensitive Potassium Channels","volume":"272","author":"Fan","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1085\/jgp.116.3.391","article-title":"Regulation of Cloned ATP-Sensitive K Channels by Phosphorylation, MgADP, and Phosphatidylinositol Bisphosphate (PIP(2)): A Study of Channel Rundown and Reactivation","volume":"116","author":"Ribalet","year":"2000","journal-title":"J. Gen. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1126\/science.270.5239.1166","article-title":"Reconstitution of IKATP: An Inward Rectifier Subunit plus the Sulfonylurea Receptor","volume":"270","author":"Inagaki","year":"1995","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s004240050559","article-title":"The Effects of Nucleotides and Potassium Channel Openers on the SUR2A\/Kir6.2 Complex K+ Channel Expressed in a Mammalian Cell Line, HEK293T Cells","volume":"435","author":"Okuyama","year":"1998","journal-title":"Pflugers Arch."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2337\/diab.45.2.113","article-title":"Mitochondria and Diabetes. Genetic, Biochemical, and Clinical Implications of the Cellular Energy Circuit","volume":"45","author":"Gerbitz","year":"1996","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1113\/jphysiol.1989.sp017765","article-title":"ATP-Sensitive K+ Channels in Rat Pancreatic Beta-Cells: Modulation by ATP and Mg2+ Ions","volume":"416","author":"Ashcroft","year":"1989","journal-title":"J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/BF00583729","article-title":"ATP4\u2212 and ATP.Mg Inhibit the ATP-Sensitive K+ Channel of Rat Ventricular Myocytes","volume":"412","author":"Findlay","year":"1988","journal-title":"Pflugers Arch."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1126\/science.272.5269.1785","article-title":"Adenosine Diphosphate as an Intracellular Regulator of Insulin Secretion","volume":"272","author":"Nichols","year":"1996","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature04711","article-title":"KATP Channels as Molecular Sensors of Cellular Metabolism","volume":"440","author":"Nichols","year":"2006","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF00232910","article-title":"Two Sites for Adenine-Nucleotide Regulation of ATP-Sensitive Potassium Channels in Mouse Pancreatic \u03b2-Cells and HIT Cells","volume":"129","author":"Hopkins","year":"1992","journal-title":"J. Membr. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/387179a0","article-title":"Truncation of Kir6.2 Produces ATP-Sensitive K+ Channels in the Absence of the Sulphonylurea Receptor","volume":"387","author":"Tucker","year":"1997","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bushman, J.D., Zhou, Q., and Shyng, S.L. (2013). A Kir6.2 Pore Mutation Causes Inactivation of ATP-Sensitive Potassium Channels by Disrupting PIP2-Dependent Gating. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063733"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1113\/jphysiol.2005.100719","article-title":"ATP-Sensitive K+ Channels: Regulation of Bursting by the Sulphonylurea Receptor, PIP2 and Regions of Kir6.2","volume":"571","author":"Ribalet","year":"2006","journal-title":"J. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1085\/jgp.110.6.643","article-title":"Regulation of KATP Channel Activity by Diazoxide and MgADP. Distinct Functions of the Two Nucleotide Binding Folds of the Sulfonylurea Receptor","volume":"110","author":"Shyng","year":"1997","journal-title":"J. Gen. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1085\/jgp.116.5.599","article-title":"Structural Determinants of Pip2 Regulation of Inward Rectifier KATP Channels","volume":"116","author":"Shyng","year":"2000","journal-title":"J. Gen. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1469-7793.1999.0325p.x","article-title":"Involvement of the N-Terminus of Kir6.2 in Coupling to the Sulphonylurea Receptor","volume":"518","author":"Reimann","year":"1999","journal-title":"J. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1126\/science.282.5391.1138","article-title":"Membrane Phospholipid Control of Nucleotide Sensitivity of KATP Channels","volume":"282","author":"Shyng","year":"1998","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1113\/JP283345","article-title":"The Dynamic Interplay of PIP2 and ATP in the Regulation of the KATP Channel","volume":"600","author":"Pipatpolkai","year":"2022","journal-title":"J. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/humu.20838","article-title":"Update of Mutations in the Genes Encoding the Pancreatic Beta-Cell K(ATP) Channel Subunits Kir6.2 (KCNJ11) and Sulfonylurea Receptor 1 (ABCC8) in Diabetes Mellitus and Hyperinsulinism","volume":"30","author":"Flanagan","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2337\/db21-0755","article-title":"ATP-Sensitive Potassium Channels in Hyperinsulinism and Type 2 Diabetes: Inconvenient Paradox or New Paradigm?","volume":"71","author":"Nichols","year":"2022","journal-title":"Diabetes"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1093\/hmg\/5.11.1813","article-title":"Mutations in the Sulonylurea Receptor Gene Are Associated with Familial Hyperinsulinism in Ashkenazi Jews","volume":"5","author":"Nestorowicz","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2478\/v10007-010-0040-9","article-title":"Genetic Polymorphisms in Diabetes: Influence on Therapy with Oral Antidiabetics","volume":"60","author":"Glamoclija","year":"2010","journal-title":"Acta Pharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/db07-1547","article-title":"A Rare Mutation in ABCC8\/SUR1 Leading to Altered ATP-Sensitive K+ Channel Activity and Beta-Cell Glucose Sensing Is Associated with Type 2 Diabetes in Adults","volume":"57","author":"Tarasov","year":"2008","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.clinbiochem.2014.12.026","article-title":"ATP-Dependent Potassium Channels and Type 2 Diabetes Mellitus","volume":"48","author":"Bonfanti","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"110667","DOI":"10.1016\/j.mce.2019.110667","article-title":"Pharmacological Chaperones of ATP-Sensitive Potassium Channels: Mechanistic Insight from CryoEM Structures","volume":"502","author":"Martin","year":"2020","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1172\/JCI25495","article-title":"ATP-Sensitive Potassium Channelopathies: Focus on Insulin Secretion","volume":"115","author":"Ashcroft","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1021\/ac990318d","article-title":"A Fluorescent Indicator for Tyrosine Phosphorylation-Based Insulin Signaling Pathways","volume":"71","author":"Sato","year":"1999","journal-title":"Anal. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1056\/NEJMoa032922","article-title":"Activating Mutations in the Gene Encoding the ATP-Sensitive Potassium-Channel Subunit Kir6.2 and Permanent Neonatal Diabetes","volume":"350","author":"Gloyn","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2337\/diab.39.11.1399","article-title":"V Sulfonylurea-Stimulated Glucose Transport Association with Diacylglycerollike Activation of Protein Kinase C in BC3H1 Myocytes","volume":"39","author":"Cooper","year":"1990","journal-title":"Diabetes"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.2337\/diab.36.11.1292","article-title":"Direct Effects of Sulfonylurea Agents on Glucose Transport in the BC3H-1 Myocyte","volume":"36","author":"Rogers","year":"1987","journal-title":"Diabetes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1172\/JCI110257","article-title":"In Vitro Effects of a Sulfonylurea on Insulin Action in Adipocytes. Potentiation of Insulin-Stimulated Hexose Transport","volume":"68","author":"Maloff","year":"1981","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1172\/JCI114170","article-title":"Coordinate Regulation of Glucose Transporter Function, Number, and Gene Expression by Insulin and Sulfonylureas in L6 Rat Skeletal Muscle Cells","volume":"84","author":"Wang","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s002329900178","article-title":"Kinetic Analysis of the Inhibitory Effect of Glibenclamide on KATP Channels of Mammalian Skeletal Muscle","volume":"155","author":"Davies","year":"1997","journal-title":"J. Membr. Biol."},{"key":"ref_80","first-page":"H313","article-title":"Effect of Tolbutamide on Myocardial Energy Metabolism","volume":"245","author":"Kramer","year":"1983","journal-title":"Am. J. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1210\/endo-110-5-1840","article-title":"Acute Tolbutamide Administration Alone or Combined with Insulin Enhances Glucose Uptake in the Perfused Rat Hindlimb","volume":"110","author":"Daniels","year":"1982","journal-title":"Endocrinology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1210\/endo.136.6.7750472","article-title":"Stimulation of Glucose Uptake and Increased Plasma Membrane Content of Glucose Transporters in L6 Skeletal Muscle Cells by the Sulfonylureas Gliclazide and Glyburide","volume":"136","author":"Tsiani","year":"1995","journal-title":"Endocrinology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/BF00400409","article-title":"Sulphonylurea Stimulates Glucose Uptake in Rats through an ATP-Sensitive K+ Channel Dependent Mechanism","volume":"39","author":"Pulido","year":"1996","journal-title":"Diabetologia"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10402","DOI":"10.1073\/pnas.95.18.10402","article-title":"Defective Insulin Secretion and Enhanced Insulin Action in KATP Channel-Deficient Mice","volume":"95","author":"Miki","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2169\/internalmedicine.41.84","article-title":"Adenosine Triphosphate-Sensitive Potassium (K(ATP)) Channel Activity Is Coupled with Insulin Resistance in Obesity and Type 2 Diabetes Mellitus","volume":"41","author":"Wasada","year":"2002","journal-title":"Intern. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2337\/diab.46.3.508","article-title":"Amino Acid Polymorphisms in the ATP-Regulatable Inward Rectifier Kir6.2 and Their Relationships to Glucose- and Tolbutamide-Induced Insulin Secretion, the Insulin Sensitivity Index, and NIDDM","volume":"46","author":"Hansen","year":"1997","journal-title":"Diabetes"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S0026-0495(99)90099-9","article-title":"Adenosine Triphosphate-Sensitive Potassium Channels Are Involved in Insulin-Mediated Glucose Transport in Humans","volume":"48","author":"Wasada","year":"1999","journal-title":"Metabolism"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1507\/endocrj.48.369","article-title":"ATP-Sensitive Potassium Channels Modulate Glucose Transport in Cultured Human Skeletal Muscle Cells","volume":"48","author":"Wasada","year":"2001","journal-title":"Endocr. J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/PL00005072","article-title":"Inhibition by Protein Kinase C of the 86Rb+ Efflux and Vasorelaxation Induced by P1075, a K(ATP) Channel Opener, in Rat Isolated Aorta","volume":"356","author":"Linde","year":"1997","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1096\/fasebj.14.3.455","article-title":"Diazoxide Down-Regulates Leptin and Lipid Metabolizing Enzymes in Adipose Tissue of Zucker Rats","volume":"14","author":"Standridge","year":"2000","journal-title":"FASEB J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1096\/fasebj.13.13.1833","article-title":"Role of the Sulfonylurea Receptor in Regulating Human Adipocyte Metabolism","volume":"13","author":"Shi","year":"1999","journal-title":"FASEB J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1210\/edrv.23.2.0461","article-title":"Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes","volume":"23","author":"Lewis","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_93","first-page":"E708","article-title":"Tissue Triglycerides, Insulin Resistance, and Insulin Production: Implications for Hyperinsulinemia of Obesity","volume":"273","author":"Koyama","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2337\/diabetes.49.5.677","article-title":"Fuel Selection in Human Skeletal Muscle in Insulin Resistance: A Reexamination","volume":"49","author":"Kelley","year":"2000","journal-title":"Diabetes"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1126\/science.2471269","article-title":"Arachidonic Acid and Other Fatty Acids Directly Activate Potassium Channels in Smooth Muscle Cells","volume":"244","author":"Ordway","year":"1989","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"10623","DOI":"10.1074\/jbc.271.18.10623","article-title":"Activation of the ATP-Sensitive K+ Channel by Long Chain Acyl-CoA. A Role in Modulation of Pancreatic Beta-Cell Glucose Sensitivity","volume":"271","author":"Larsson","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_97","first-page":"R1223","article-title":"Brain Glucose Sensing and Body Energy Homeostasis: Role in Obesity and Diabetes","volume":"276","author":"Levin","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0361-9230(85)90041-3","article-title":"Actions of Feeding-Relevant Agents on Hypothalamic Glucose-Responsive Neurons in Vitro","volume":"15","author":"Kow","year":"1985","journal-title":"Brain Res. Bull."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0006-8993(84)90466-9","article-title":"Glucose Responding Neurons in the Nucleus Tractus Solitarius of the Rat: In Vitro Study","volume":"307","author":"Mizuno","year":"1984","journal-title":"Brain Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/247284a0","article-title":"Glucose Inhibition of the Glucose-Sensitive Neurone in the Rat Lateral Hypothalamus","volume":"247","author":"Oomura","year":"1974","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0006-8993(98)00956-1","article-title":"Distribution and Phenotype of Neurons Containing the ATP-Sensitive K+ Channel in Rat Brain","volume":"814","author":"Rawson","year":"1998","journal-title":"Brain Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1476-5381.1990.tb14116.x","article-title":"Tolbutamide Excites Rat Glucoreceptive Ventromedial Hypothalamic Neurones by Indirect Inhibition of ATP-K+ Channels","volume":"101","author":"Ashford","year":"1990","journal-title":"Br. J. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1016\/S0021-9258(17)41910-7","article-title":"Analysis of Upstream Glucokinase Promoter Activity in Transgenic Mice and Identification of Glucokinase in Rare Neuroendocrine Cells in the Brain and Gut","volume":"269","author":"Jetton","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.2337\/diabetes.50.10.2203","article-title":"The Effect of Insulin on in Vivo Cerebral Glucose Concentrations and Rates of Glucose Transport\/Metabolism in Humans","volume":"50","author":"Seaquist","year":"2001","journal-title":"Diabetes"},{"key":"ref_105","first-page":"387","article-title":"Insulin in the Brain: A Hormonal Regulator of Energy Balance","volume":"13","author":"Schwartz","year":"1992","journal-title":"Endocr. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/(SICI)1096-9861(19991206)415:1<105::AID-CNE8>3.0.CO;2-H","article-title":"Region-Specific MRNA Expression of Phosphatidylinositol 3-Kinase Regulatory Isoforms in the Central Nervous System of C57BL\/6J Mice","volume":"415","author":"Kahn","year":"1999","journal-title":"J. Comp. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1172\/JCI24445","article-title":"The Role of Insulin Receptor Substrate 2 in Hypothalamic and Beta Cell Function","volume":"115","author":"Choudhury","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"S174","DOI":"10.2337\/dc09-S305","article-title":"Where Does Insulin Resistance Start? The Brain","volume":"32","author":"Pagotto","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1126\/science.289.5487.2122","article-title":"Role of Brain Insulin Receptor in Control of Body Weight and Reproduction","volume":"289","author":"Gautam","year":"2000","journal-title":"Science"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nn0602-861","article-title":"Decreasing Hypothalamic Insulin Receptors Causes Hyperphagia and Insulin Resistance in Rats","volume":"5","author":"Obici","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/nm1202-798","article-title":"Hypothalamic Insulin Signaling Is Required for Inhibition of Glucose Production","volume":"8","author":"Obici","year":"2002","journal-title":"Nat. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/nature03439","article-title":"Hypothalamic K(ATP) Channels Control Hepatic Glucose Production","volume":"434","author":"Pocai","year":"2005","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"12103","DOI":"10.1073\/pnas.0604404103","article-title":"The Cerebrocortical Response to Hyperinsulinemia Is Reduced in Overweight Humans: A Magnetoencephalographic Study","volume":"103","author":"Tschritter","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/4079\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:24:10Z","timestamp":1760106250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/4079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,6]]},"references-count":113,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25074079"],"URL":"https:\/\/doi.org\/10.3390\/ijms25074079","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,6]]}}}