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This review focuses on the Ca<jats:sup>2+<\/jats:sup>-regulated K<jats:sup>+<\/jats:sup> channel K<jats:sub>Ca<\/jats:sub>3.1, encoded by the <jats:italic>KCNN4<\/jats:italic> gene, which is present in both parts of the pancreas. In the islets of Langerhans, K<jats:sub>Ca<\/jats:sub>3.1 channels are involved in the regulation of membrane potential oscillations characterizing nutrient-stimulated islet activity. Channel upregulation is induced by gluco- or lipotoxic conditions and might contribute to micro-inflammation and impaired insulin release in type 2 diabetes mellitus as well as to diabetes-associated renal and vascular complications. In the exocrine pancreas K<jats:sub>Ca<\/jats:sub>3.1 channels are expressed in acinar and ductal cells. They are thought to play a role for anion secretion during digestion but their physiological role has not been fully elucidated yet. Pancreatic carcinoma, especially pancreatic ductal adenocarcinoma (PDAC), is associated with drastic overexpression of K<jats:sub>Ca<\/jats:sub>3.1. For pharmacological targeting of K<jats:sub>Ca<\/jats:sub>3.1 channels, we are discussing the possible benefits K<jats:sub>Ca<\/jats:sub>3.1 channel inhibitors might provide in the context of diabetes mellitus and pancreatic cancer, respectively. We are also giving a perspective for the use of a fluorescently labeled derivative of the K<jats:sub>Ca<\/jats:sub>3.1 blocker senicapoc as a tool to monitor channel distribution in pancreatic tissue. In summary, modulating K<jats:sub>Ca<\/jats:sub>3.1 channel activity is a useful strategy for exo-and endocrine pancreatic disease but further studies are needed to evaluate its clinical suitability.<\/jats:p>","DOI":"10.1515\/hsz-2022-0232","type":"journal-article","created":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T14:20:52Z","timestamp":1672064452000},"page":"339-353","source":"Crossref","is-referenced-by-count":9,"title":["Pancreatic K<sub>Ca<\/sub>3.1 channels in health and disease"],"prefix":"10.1515","volume":"404","author":[{"given":"Benjamin","family":"Soret","sequence":"first","affiliation":[{"name":"University of M\u00fcnster, Institute of Physiology II , Robert-Koch-Stra\u00dfe 27b, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurek","family":"Hense","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster, Institute of Pharmaceutical and Medicinal Chemistry , Department of Pharmacology , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"L\u00fcdtke","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster, Institute of Pharmaceutical and Medicinal Chemistry , Department of Pharmacology , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insa","family":"Thale","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster, Institute of Pharmaceutical and Medicinal Chemistry , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht","family":"Schwab","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster, Institute of Physiology II , Robert-Koch-Stra\u00dfe 27b, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1572-9235","authenticated-orcid":false,"given":"Martina","family":"D\u00fcfer","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster, Institute of Pharmaceutical and Medicinal Chemistry , Department of Pharmacology , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"2023033110335740536_j_hsz-2022-0232_ref_001","doi-asserted-by":"crossref","unstructured":"Andersen, D.K., Korc, M., Petersen, G.M., Eibl, G., Li, D., Rickels, M.R., Chari, S.T., and Abbruzzese, J.L. (2017). Diabetes, pancreatogenic diabetes, and pancreatic cancer. Diabetes 66: 1103\u20131110, https:\/\/doi.org\/10.2337\/db16-1477.","DOI":"10.2337\/db16-1477"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_002","doi-asserted-by":"crossref","unstructured":"Apte, M.V., Pirola, R.C., and Wilson, J.S. (2012). Pancreatic stellate cells: a starring role in normal and diseased pancreas. Front. Physiol. 3: 344, https:\/\/doi.org\/10.3389\/fphys.2012.00344.","DOI":"10.3389\/fphys.2012.00344"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_003","doi-asserted-by":"crossref","unstructured":"Arnush, M., Heitmeier, M.R., Scarim, A.L., Marino, M.H., Manning, P.T., and Corbett, J.A. (1998). IL-1 produced and released endogenously within\u00a0human islets inhibits beta cell function. J.\u00a0Clin. Invest. 102: 516\u2013526, https:\/\/doi.org\/10.1172\/jci844.","DOI":"10.1172\/JCI844"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_004","doi-asserted-by":"crossref","unstructured":"Ataga, K.I., Smith, W.R., Castro, L.M.de, Swerdlow, P., Saunthararajah, Y., Castro, O., Vichinsky, E., Kutlar, A., Orringer, E.P., Rigdon, G.C., et al.. (2008). Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood 111: 3991\u20133997, https:\/\/doi.org\/10.1182\/blood-2007-08-110098.","DOI":"10.1182\/blood-2007-08-110098"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_005","doi-asserted-by":"crossref","unstructured":"Backx, E., Coolens, K., van den Bossche, J.L., Houbracken, I., Espinet, E., and Rooman, I. (2022). On the origin of pancreatic cancer: molecular tumor subtypes in perspective of exocrine cell plasticity. Cell. Mol. Gastroenterol. Hepatol. 13: 1243\u20131253, https:\/\/doi.org\/10.1016\/j.jcmgh.2021.11.010.","DOI":"10.1016\/j.jcmgh.2021.11.010"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_006","doi-asserted-by":"crossref","unstructured":"Blaszczak, W. and Swietach, P. (2021). What do cellular responses to acidity tell us about cancer? Cancer Metastasis Rev. 40: 1159\u20131176, https:\/\/doi.org\/10.1007\/s10555-021-10005-3.","DOI":"10.1007\/s10555-021-10005-3"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_007","doi-asserted-by":"crossref","unstructured":"B\u00f6ni-Schnetzler, M., Thorne, J., Parnaud, G., Marselli, L., Ehses, J.A., Kerr-Conte, J., Pattou, F., Halban, P.A., Weir, G.C., and Donath, M.Y. (2008). Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J.\u00a0Clin. Endocrinol. Metab. 93: 4065\u20134074, https:\/\/doi.org\/10.1210\/jc.2008-0396.","DOI":"10.1210\/jc.2008-0396"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_008","doi-asserted-by":"crossref","unstructured":"Bonito, B., Sauter, D.R.P., Schwab, A., Djamgoz, M.B.A., and Novak, I. (2016). KCa3.1 (IK) modulates pancreatic cancer cell migration, invasion and proliferation: anomalous effects on TRAM-34. Pflugers. Arch. 468: 1865\u20131875, https:\/\/doi.org\/10.1007\/s00424-016-1891-9.","DOI":"10.1007\/s00424-016-1891-9"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_009","doi-asserted-by":"crossref","unstructured":"Br\u00f6mmel, K., Maskri, S., Maisuls, I., Konken, C.P., Rieke, M., Peth\u0151, Z., Strassert, C.A., Koch, O., Schwab, A., and W\u00fcnsch, B. (2020). Synthesis of small-molecule fluorescent probes for the in\u00a0vitro imaging of calcium-activated potassium channel KCa 3.1. Angew Chem. Int. Ed. Engl. 59: 8277\u20138284, https:\/\/doi.org\/10.1002\/ange.202001201.","DOI":"10.1002\/anie.202001201"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_010","doi-asserted-by":"crossref","unstructured":"Brown, B.M., Pressley, B., and Wulff, H. (2018). KCa3.1 channel modulators as potential therapeutic compounds for glioblastoma. Curr. Neuropharmacol. 16: 618\u2013626, https:\/\/doi.org\/10.2174\/1570159x15666170630164226.","DOI":"10.2174\/1570159X15666170630164226"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_011","doi-asserted-by":"crossref","unstructured":"Bulk, E., Todesca, L.M., Bachmann, M., Szabo, I., Rieke, M., and Schwab, A. (2022). Functional expression of mitochondrial KCa3.1 channels in non-small cell lung cancer cells. Pfl\u00fcgers. Arch. 474: 1147\u20131157, https:\/\/doi.org\/10.1007\/s00424-022-02748-x.","DOI":"10.1007\/s00424-022-02748-x"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_012","doi-asserted-by":"crossref","unstructured":"Burke, S.J., Karlstad, M.D., Regal, K.M., Sparer, T.E., Lu, D., Elks, C.M., Grant, R.W., Stephens, J.M., Burk, D.H., and Collier, J.J. (2015). CCL20 is elevated during obesity and differentially regulated by NF-\u03baB subunits in pancreatic \u03b2-cells. Biochim. Biophys. Acta 1849: 637\u2013652, https:\/\/doi.org\/10.1016\/j.bbagrm.2015.03.007.","DOI":"10.1016\/j.bbagrm.2015.03.007"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_013","doi-asserted-by":"crossref","unstructured":"Chimote, A.A., Balajthy, A., Arnold, M.J., Newton, H.S., Hajdu, P., Qualtieri, J., Wise-Draper, T., and Conforti, L. (2018). A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment. Sci. 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Chem. 80: 3728\u20133735, https:\/\/doi.org\/10.1021\/ac800164v.","DOI":"10.1021\/ac800164v"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_021","doi-asserted-by":"crossref","unstructured":"Fanger, C.M., Ghanshani, S., Logsdon, N.J., Rauer, H., Kalman, K., Zhou, J., Beckingham, K., Chandy, K.G., Cahalan, M.D., and Aiyar, J. (1999). Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel IKCa1. J.\u00a0Biol. Chem. 274: 5746\u20135754, https:\/\/doi.org\/10.1074\/jbc.274.9.5746.","DOI":"10.1074\/jbc.274.9.5746"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_022","doi-asserted-by":"crossref","unstructured":"Garg, B., Giri, B., Modi, S., Sethi, V., Castro, I., Umland, O., Ban, Y., Lavania, S., Dawra, R., Banerjee, S., et al.. (2018). NF-\u03baB in pancreatic stellate cells reduces infiltration of tumors by cytotoxic T\u00a0cells and killing of cancer cells, via up-regulation of CXCL12. Gastroenterology 155: 880\u2013891.e8, https:\/\/doi.org\/10.1053\/j.gastro.2018.05.051.","DOI":"10.1053\/j.gastro.2018.05.051"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_023","doi-asserted-by":"crossref","unstructured":"Gerlach, A.C., Gangopadhyay, N.N., and Devor, D.C. (2000). Kinase-dependent regulation of the intermediate conductance, calcium-dependent potassium channel hIK1. J.\u00a0Biol. Chem. 275: 585\u2013598, https:\/\/doi.org\/10.1074\/jbc.275.1.585.","DOI":"10.1074\/jbc.275.1.585"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_024","doi-asserted-by":"crossref","unstructured":"Ghanshani, S., Wulff, H., Miller, M.J., Rohm, H., Neben, A., Gutman, G.A., Cahalan, M.D., and Chandy, K.G. (2000). Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences. J.\u00a0Biol. 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Cancer Cell 21: 418\u2013429, https:\/\/doi.org\/10.1016\/j.ccr.2012.01.007.","DOI":"10.1016\/j.ccr.2012.01.007"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_080","doi-asserted-by":"crossref","unstructured":"Rabjerg, M., Oliv\u00e1n-Viguera, A., Hansen, L.K., Jensen, L., Sevelsted-M\u00f8ller, L., Walter, S., Jensen, B.L., Marcussen, N., and K\u00f6hler, R. (2015). High expression of KCa3.1 in patients with clear cell renal carcinoma predicts high metastatic risk and poor survival. PLoS One 10: e0122992, https:\/\/doi.org\/10.1371\/journal.pone.0122992.","DOI":"10.1371\/journal.pone.0122992"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_081","doi-asserted-by":"crossref","unstructured":"Rorsman, P. and Ashcroft, F.M. (2018). Pancreatic \u03b2-cell electrical activity\u00a0and insulin secretion: of mice and men. Physiol. 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Oncotarget 8: 41432\u201341439, https:\/\/doi.org\/10.18632\/oncotarget.18186.","DOI":"10.18632\/oncotarget.18186"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_086","doi-asserted-by":"crossref","unstructured":"Shin, S.H., Kim, S.C., Hong, S.M., Kim, Y.H., Song, K.B., Park, K.M., and Lee, Y.J. (2013). Genetic alterations of K-ras, p53, c-erbB-2, and DPC4 in pancreatic ductal adenocarcinoma and their correlation with patient survival. Pancreas 42: 216\u2013222, https:\/\/doi.org\/10.1097\/mpa.0b013e31825b6ab0.","DOI":"10.1097\/MPA.0b013e31825b6ab0"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_087","doi-asserted-by":"crossref","unstructured":"Sikimic, J., Hoffmeister, T., Gresch, A., Kaiser, J., Barthlen, W., Wolke, C., Wieland, I., Lendeckel, U., Krippeit-Drews, P., D\u00fcfer, M., et al.. (2020). Possible new strategies for the treatment of congenital hyperinsulinism. Front. 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Oncotarget 8: 769\u2013784, https:\/\/doi.org\/10.18632\/oncotarget.13647.","DOI":"10.18632\/oncotarget.13647"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_094","doi-asserted-by":"crossref","unstructured":"Strupp, M., Staub, F., and Grafe, P. (1993). A Ca2+-and pH-dependent K+ channel of rat C6 glioma cells and its possible role in acidosis-induced cell swelling. Glia 9: 136\u2013145, https:\/\/doi.org\/10.1002\/glia.440090207.","DOI":"10.1002\/glia.440090207"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_095","doi-asserted-by":"crossref","unstructured":"Su, X.L., Wang, Y., Zhang, W., Zhao, L.M., Li, G.R., and Deng, X.L. (2011). Insulin-mediated upregulation of K (Ca) 3.1 channels promotes cell migration and proliferation in rat vascular smooth muscle. J.\u00a0Mol. Cell. Cardiol. 51: 51\u201357, https:\/\/doi.org\/10.1016\/j.yjmcc.2011.03.014.","DOI":"10.1016\/j.yjmcc.2011.03.014"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_096","doi-asserted-by":"crossref","unstructured":"Sweed, D., Taha, M., Elhamed, S.A., and Mohamed, A.S.E.D. (2022). The prognostic role of CD73\/A2AR expression and tumor immune response in periampullary carcinoma subtypes. Asian Pac. J.\u00a0Cancer Prev. APJCP 23: 1239\u20131246, https:\/\/doi.org\/10.31557\/apjcp.2022.23.4.1239.","DOI":"10.31557\/APJCP.2022.23.4.1239"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_097","doi-asserted-by":"crossref","unstructured":"Szabo, I. and Zoratti, M. (2014). Mitochondrial channels: ion fluxes and more. Physiol. Rev. 94: 519\u2013608, https:\/\/doi.org\/10.1152\/physrev.00021.2013.","DOI":"10.1152\/physrev.00021.2013"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_098","doi-asserted-by":"crossref","unstructured":"Tamarina, N.A., Wang, Y., Mariotto, L., Kuznetsov, A., Bond, C., Adelman, J., and Philipson, L.H. (2003). Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses. Diabetes 52: 2000\u20132006, https:\/\/doi.org\/10.2337\/diabetes.52.8.2000.","DOI":"10.2337\/diabetes.52.8.2000"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_099","doi-asserted-by":"crossref","unstructured":"Tao, J., Yang, G., Zhou, W., Qiu, J., Chen, G., Luo, W., Zhao, F., You, L., Zheng, L., Zhang, T., et al.. (2021). Targeting hypoxic tumor microenvironment in pancreatic cancer. J.\u00a0Hematol. Oncol. 14: 14, https:\/\/doi.org\/10.1186\/s13045-020-01030-w.","DOI":"10.1186\/s13045-020-01030-w"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_100","doi-asserted-by":"crossref","unstructured":"Tesch, G.H. (2008). MCP-1\/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am. J.\u00a0Physiol. Ren. Physiol. 294: F697\u2013F701, https:\/\/doi.org\/10.1152\/ajprenal.00016.2008.","DOI":"10.1152\/ajprenal.00016.2008"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_101","doi-asserted-by":"crossref","unstructured":"Thompson-Vest, N., Shimizu, Y., Hunne, B., and Furness, J.B. (2006). The distribution of intermediate-conductance, calcium-activated, potassium (IK) channels in epithelial cells. J.\u00a0Anat. 208: 219\u2013229, https:\/\/doi.org\/10.1111\/j.1469-7580.2006.00515.x.","DOI":"10.1111\/j.1469-7580.2006.00515.x"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_102","doi-asserted-by":"crossref","unstructured":"Todesca, L.M., Maskri, S., Br\u00f6mmel, K., Thale, I., W\u00fcnsch, B., Koch, O., and Schwab, A. (2021). Targeting Kca3.1 channels in cancer. Cell. Physiol. Biochem. 55: 131\u2013144, https:\/\/doi.org\/10.33594\/000000374.","DOI":"10.33594\/000000374"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_103","doi-asserted-by":"crossref","unstructured":"Wang, J., Haanes, K.A., and Novak, I. (2013). Purinergic regulation of CFTR and Ca (2+)-activated Cl (-) channels and K (+) channels in human pancreatic duct epithelium. Am. J.\u00a0Physiol. Cell Physiol. 304: C673\u2013C684, https:\/\/doi.org\/10.1152\/ajpcell.00196.2012.","DOI":"10.1152\/ajpcell.00196.2012"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_104","doi-asserted-by":"crossref","unstructured":"Welsh, N., Cnop, M., Kharroubi, I., Bugliani, M., Lupi, R., Marchetti, P., and Eizirik, D.L. (2005). Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets? Diabetes 54: 3238\u20133244, https:\/\/doi.org\/10.2337\/diabetes.54.11.3238.","DOI":"10.2337\/diabetes.54.11.3238"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_105","doi-asserted-by":"crossref","unstructured":"Wong, R. and Schlichter, L.C. (2014). PKA reduces the rat and human KCa3.1 current, CaM binding, and Ca2+ signaling, which requires Ser332\/334 in the CaM-binding C terminus. J.\u00a0Neurosci. 34: 13371\u201313383, https:\/\/doi.org\/10.1523\/jneurosci.1008-14.2014.","DOI":"10.1523\/JNEUROSCI.1008-14.2014"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_106","doi-asserted-by":"crossref","unstructured":"Wulf, A. and Schwab, A. (2002). Regulation of a calcium-sensitive K+ channel (cIK1) by protein kinase C. J.\u00a0Membr. Biol. 187: 71\u201379, https:\/\/doi.org\/10.1007\/s00232-001-0149-3.","DOI":"10.1007\/s00232-001-0149-3"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_107","doi-asserted-by":"crossref","unstructured":"Wulff, H., Knaus, H.G., Pennington, M., and Chandy, K.G. (2004). K+ channel\u00a0expression during B\u00a0cell differentiation: implications for immunomodulation and autoimmunity. J.\u00a0Immunol. 173: 776\u2013786, https:\/\/doi.org\/10.4049\/jimmunol.173.2.776.","DOI":"10.4049\/jimmunol.173.2.776"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_108","doi-asserted-by":"crossref","unstructured":"Wulff, H., Miller, M.J., Hansel, W., Grissmer, S., Cahalan, M.D., and Chandy, K.G. (2000). Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant. Proc. Natl. Acad. Sci. USA 97: 8151\u20138156, https:\/\/doi.org\/10.1073\/pnas.97.14.8151.","DOI":"10.1073\/pnas.97.14.8151"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_109","doi-asserted-by":"crossref","unstructured":"Xu, R., Li, C., Wu, Y., Shen, L., Ma, J., Qian, J., and Ge, J. (2017). Role of KCa3.1 channels in macrophage polarization and its relevance in atherosclerotic plaque instability. Arterioscler. Thromb. Vasc. Biol. 37: 226\u2013236, https:\/\/doi.org\/10.1161\/atvbaha.116.308461.","DOI":"10.1161\/ATVBAHA.116.308461"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_110","doi-asserted-by":"crossref","unstructured":"Zaccagnino, A., Pilarsky, C., Tawfik, D., Sebens, S., Trauzold, A., Novak, I., Schwab, A., and Kalthoff, H. (2016). In silico analysis of the transportome in human pancreatic ductal adenocarcinoma. Eur. Biophys. J. 45: 749\u2013763, https:\/\/doi.org\/10.1007\/s00249-016-1171-9.","DOI":"10.1007\/s00249-016-1171-9"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_111","doi-asserted-by":"crossref","unstructured":"Zhang, A.M.Y., Magrill, J., Winter, T.J.J.de, Hu, X., Skovs\u00f8, S., Schaeffer, D.F., Kopp, J.L., and Johnson, J.D. (2019). Endogenous hyperinsulinemia contributes to pancreatic cancer development. Cell Metabol. 30: 403\u2013404, https:\/\/doi.org\/10.1016\/j.cmet.2019.07.003.","DOI":"10.1016\/j.cmet.2019.07.003"},{"key":"2023033110335740536_j_hsz-2022-0232_ref_112","doi-asserted-by":"crossref","unstructured":"Zhang, M., Houamed, K., Kupershmidt, S., Roden, D., and Satin, L.S. (2005). Pharmacological properties and functional role of Kslow current in mouse pancreatic beta-cells: SK channels contribute to Kslow tail current and modulate insulin secretion. J.\u00a0Gen. 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