Stimulatory effect of imeglimin on incretin secretion.

Content Provider	Europe PMC
Author	Yingyue, Quan Sugawara, Kenji Takahashi, Harumi Yokoi, Norihide Ohbayashi, Kento Iwasaki, Yusaku Seino, Susumu Ogawa, Wataru
Abstract	Aims/IntroductionImeglimin is a new antidiabetic drug structurally related to metformin. Despite this structural similarity, only imeglimin augments glucose‐stimulated insulin secretion (GSIS), with the mechanism underlying this effect remaining unclear. Given that glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) also enhance GSIS, we examined whether these incretin hormones might contribute to the pharmacological actions of imeglimin.Materials and MethodsBlood glucose and plasma insulin, GIP, and GLP‐1 concentrations were measured during an oral glucose tolerance test (OGTT) performed in C57BL/6JJcl (C57BL/6) or KK‐Ay/TaJcl (KK‐Ay) mice after administration of a single dose of imeglimin with or without the dipeptidyl peptidase‐4 inhibitor sitagliptin or the GLP‐1 receptor antagonist exendin‐9. The effects of imeglimin, with or without GIP or GLP‐1, on GSIS were examined in C57BL/6 mouse islets.ResultsImeglimin lowered blood glucose and increased plasma insulin levels during an OGTT in both C57BL/6 and KK‐Ay mice, whereas it also increased the plasma levels of GIP and GLP‐1 in KK‐Ay mice and the GLP‐1 levels in C57BL/6 mice. The combination of imeglimin and sitagliptin increased plasma insulin and GLP‐1 levels during the OGTT in KK‐Ay mice to a markedly greater extent than did either drug alone. Imeglimin enhanced GSIS in an additive manner with GLP‐1, but not with GIP, in mouse islets. Exendin‐9 had only a minor inhibitory effect on the glucose‐lowering action of imeglimin during the OGTT in KK‐Ay mice.ConclusionsOur data suggest that the imeglimin‐induced increase in plasma GLP‐1 levels likely contributes at least in part to its stimulatory effect on insulin secretion.
Page Count	755
ISSN	20401116
Journal	Journal of Diabetes Investigation
Volume Number	14
PubMed Central reference number	PMC10204172
Issue Number	6
PubMed reference number	36977210
e-ISSN	20401124
DOI	10.1111/jdi.14001
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2023-03-28
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Subject Keyword	Glucagon‐like peptide‐1 Glucose‐stimulated insulin secretion Imeglimin
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Internal Medicine