{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:17:48Z","timestamp":1792657068043,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K18012"],"award-info":[{"award-number":["19K18012"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08525"],"award-info":[{"award-number":["18K08525"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08524"],"award-info":[{"award-number":["18K08524"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/Introduction<\/jats:title>\n                    <jats:p>Imeglimin is a novel oral hypoglycemic agent that improves blood glucose levels through multiple mechanisms of action including the enhancement of glucose\u2010stimulated insulin secretion (GSIS), however, the details of this mechanism have not been clarified. In the process of GSIS, activation of the transient receptor potential melastatin 2 (TRPM2) channel, a type of non\u2010selective cation channel (NSCCs) in \u03b2\u2010cells, promotes plasma membrane depolarization. The present study aimed to examine whether imeglimin potentiates GSIS via the TRPM2 channel in \u03b2\u2010cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Pancreatic islets were isolated by collagenase digestion from male wild\u2010type and TRPM2\u2010knockout (KO) mice. Insulin release and nicotinamide adenine dinucleotide (NAD\n                      <jats:sup>+<\/jats:sup>\n                      ) production in islets were measured under static incubation. NSCC currents in mouse single \u03b2\u2010cells were measured by patch\u2010clamp experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Batch\u2010incubation studies showed that imeglimin enhanced GSIS at stimulatory 16.6 mM glucose, whereas it did not affect basal insulin levels at 2.8 mM glucose. Imeglimin increased the glucose\u2010induced production of NAD\n                      <jats:sup>+<\/jats:sup>\n                      , a precursor of cADPR, in islets and the insulinotropic effects of imeglimin were attenuated by a cADPR inhibitor 8\u2010Br\u2010cADPR. Furthermore, imeglimin increased NSCC current in \u03b2\u2010cells, and abolished this current in TRPM2\u2010KO mice. Imeglimin did not potentiate GSIS in the TRPM2\u2010KO islets, suggesting that imeglimin\u2019s increase of NSCC currents through the TRPM2 channel is causally implicated in its insulin releasing effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Imeglimin may activate TRPM2 channels in \u03b2\u2010cells via the production of NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/cADPR, leading to the potentiation of GSIS. Developing approaches to stimulate cADPR\u2010TRPM2 signaling provides a potential therapeutic tool to treat type 2 diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.13669","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T04:06:01Z","timestamp":1631678761000},"page":"34-41","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A novel mechanism of imeglimin\u2010mediated insulin secretion via the cADPR\u2010TRP channel pathway"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3323-1310","authenticated-orcid":false,"given":"Shunsuke","family":"Funazaki","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Endocrinology and Metabolism Jichi Medical University Saitama Medical Center Saitama 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