Stimulatory effect of imeglimin on incretin secretion

IF 3.2 3区 医学 Journal of Diabetes Investigation Pub Date : 2023-03-28 DOI:10.1111/jdi.14001
Quan Yingyue, Kenji Sugawara, Harumi Takahashi, Norihide Yokoi, Kento Ohbayashi, Yusaku Iwasaki, Susumu Seino, Wataru Ogawa
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引用次数: 3

Abstract

Aims/Introduction

Imeglimin 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 Methods

Blood 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.

Results

Imeglimin 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.

Conclusions

Our 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.

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伊米霉素对肠促胰岛素分泌的刺激作用
目的/介绍依米明是一种与二甲双胍结构相关的新型降糖药物。尽管有这种结构上的相似性,但只有依米霉素增加了葡萄糖刺激胰岛素分泌(GSIS),这种作用的机制尚不清楚。鉴于葡萄糖依赖性胰岛素性多肽(GIP)和胰高血糖素样肽-1 (GLP-1)也能增强GSIS,我们研究了这些肠促胰岛素激素是否可能有助于伊米霉素的药理作用。材料与方法C57BL/6JJcl (C57BL/6)或KK-Ay/TaJcl (KK-Ay)小鼠口服糖耐量试验(OGTT)时,分别在给予单剂量伊美霉素加或不加二肽基肽酶-4抑制剂西格列汀或GLP-1受体拮抗剂exendin-9后,测定血糖和血浆胰岛素、GIP和GLP-1浓度。在C57BL/6小鼠胰岛中检测了伊米霉素(含或不含GIP或GLP-1)对GSIS的影响。结果在OGTT过程中,imimimin降低了C57BL/6和KK-Ay小鼠的血糖,升高了血浆胰岛素水平,同时增加了KK-Ay小鼠血浆GIP和GLP-1水平以及C57BL/6小鼠血浆GLP-1水平。在KK-Ay小鼠OGTT期间,伊美霉素和西格列汀联合用药显著提高血浆胰岛素和GLP-1水平,其程度明显高于单独用药。在小鼠胰岛中,依米霉素可与GLP-1联合增强GSIS,但不与GIP联合。在KK-Ay小鼠OGTT过程中,Exendin-9对依米霉素的降血糖作用只有轻微的抑制作用。结论:我们的数据表明,imigelimo诱导的血浆GLP-1水平升高可能至少部分地促进了胰岛素分泌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation Medicine-Internal Medicine
自引率
9.40%
发文量
218
期刊介绍: Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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