{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T11:57:14Z","timestamp":1783857434095,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Imeglimin is a new antidiabetic drug structurally related to metformin. Despite this structural similarity, only imeglimin augments glucose\u2010stimulated insulin secretion (GSIS), with the mechanism underlying this effect remaining unclear. Given that glucose\u2010dependent insulinotropic polypeptide (GIP) and glucagon\u2010like peptide\u20101 (GLP\u20101) also enhance GSIS, we examined whether these incretin hormones might contribute to the pharmacological actions of imeglimin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Blood glucose and plasma insulin, GIP, and GLP\u20101 concentrations were measured during an oral glucose tolerance test (OGTT) performed in C57BL\/6JJcl (C57BL\/6) or KK\u2010Ay\/TaJcl (KK\u2010Ay) mice after administration of a single dose of imeglimin with or without the dipeptidyl peptidase\u20104 inhibitor sitagliptin or the GLP\u20101 receptor antagonist exendin\u20109. The effects of imeglimin, with or without GIP or GLP\u20101, on GSIS were examined in C57BL\/6 mouse islets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Imeglimin lowered blood glucose and increased plasma insulin levels during an OGTT in both C57BL\/6 and KK\u2010Ay mice, whereas it also increased the plasma levels of GIP and GLP\u20101 in KK\u2010Ay mice and the GLP\u20101 levels in C57BL\/6 mice. The combination of imeglimin and sitagliptin increased plasma insulin and GLP\u20101 levels during the OGTT in KK\u2010Ay mice to a markedly greater extent than did either drug alone. Imeglimin enhanced GSIS in an additive manner with GLP\u20101, but not with GIP, in mouse islets. Exendin\u20109 had only a minor inhibitory effect on the glucose\u2010lowering action of imeglimin during the OGTT in KK\u2010Ay mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data suggest that the imeglimin\u2010induced increase in plasma GLP\u20101 levels likely contributes at least in part to its stimulatory effect on insulin secretion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14001","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T19:43:42Z","timestamp":1680032622000},"page":"746-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Stimulatory effect of imeglimin on incretin secretion"],"prefix":"10.1111","volume":"14","author":[{"given":"Quan","family":"Yingyue","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine Kobe University Graduate School of Medicine  Kobe 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