Imeglimin 可通过间接机制增强胰高血糖素分泌,并改善高脂高蔗糖饮食喂养小鼠的脂肪肝。

IF 3.1 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Osamu Kikuchi, Yuichi Ikeuchi, Masaki Kobayashi, Yoko Tabei, Hiromi Yokota-Hashimoto, Tadahiro Kitamura
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引用次数: 0

摘要

目的/引言伊迈格列明是最近批准的一种口服抗糖尿病药物,可改善胰岛素抵抗,促进胰岛β细胞分泌胰岛素。在此,我们研究了伊迈格列明对胰腺α细胞分泌胰高血糖素的影响:实验在高脂肪、高蔗糖饮食喂养的小鼠中进行。使用胰岛素和葡萄糖耐量试验、葡萄糖钳夹研究以及离体胰岛胰高血糖素分泌测量来检验伊麦角林的作用。胰高血糖素的测定采用标准方案和 Mercodia 夹心酶联免疫吸附试验的顺序方案;后者消除了与其他胰高血糖素衍生肽的交叉反应:结果:给高脂肪、高蔗糖饮食喂养的小鼠注射伊麦角林后,血浆中胰高血糖素、胰岛素和胰高血糖素样肽-1的水平升高。葡萄糖钳夹实验表明,胰高血糖素的升高不是由血糖水平降低引起的。在单次和长期服用伊麦格列明后,葡萄糖耐量试验中的胰高血糖素分泌明显增强。使用连续给药方案时,胰高血糖素分泌增强的程度较轻。长期服用伊迈格列明不会改变α细胞质量。腹腔注射伊迈格列明不会影响胰高血糖素的分泌,尽管血糖水平明显下降。伊麦格列明不会增强离体胰岛分泌胰高血糖素。服用伊迈格列明可通过减少固醇调节元件结合蛋白-1c和碳水化合物反应元件结合蛋白及其靶基因来抑制新脂肪生成,同时通过增加肉碱棕榈酰基转移酶I来促进脂肪酸氧化,从而改善脂肪肝:总之,本研究结果表明,伊麦角林通过间接机制促进胰高血糖素分泌。我们的研究结果还表明,伊麦角林促进的胰高血糖素分泌可通过抑制新脂肪生成和促进脂肪酸氧化来改善脂肪肝。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice

Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice

Aims/Introduction

Imeglimin is a recently approved oral antidiabetic agent that improves insulin resistance, and promotes insulin secretion from pancreatic β-cells. Here, we investigated the effects of imeglimin on glucagon secretion from pancreatic α-cells.

Materials and Methods

Experiments were carried out in high-fat, high-sucrose diet-fed mice. The effects of imeglimin were examined using insulin and glucose tolerance tests, glucose clamp studies, and measurements of glucagon secretion from isolated islets. Glucagon was measured using both the standard and the sequential protocol of Mercodia sandwich enzyme-linked immunosorbent assay; the latter eliminates cross-reactivities with other proglucagon-derived peptides.

Results

Plasma glucagon, insulin and glucagon-like peptide-1 levels were increased by imeglimin administration in high-fat, high-sucrose diet-fed mice. Glucose clamp experiments showed that the glucagon increase was not caused by reduced blood glucose levels. After both single and long-term administration of imeglimin, glucagon secretions were significantly enhanced during glucose tolerance tests. Milder enhancement was observed when using the sequential protocol. Long-term administration of imeglimin did not alter α-cell mass. Intraperitoneal imeglimin administration did not affect glucagon secretion, despite significantly decreased blood glucose levels. Imeglimin did not enhance glucagon secretion from isolated islets. Imeglimin administration improved fatty liver by suppressing de novo lipogenesis through decreasing sterol regulatory element binding protein-1c and carbohydrate response element binding protein and their target genes, while enhancing fatty acid oxidation through increasing carnitine palmitoyltransferase I.

Conclusions

Overall, the present results showed that imeglimin enhances glucagon secretion through an indirect mechanism. Our findings also showed that glucagon secretion promoted by imeglimin could contribute to improvement of fatty liver through suppressing de novo lipogenesis and enhancing fatty acid oxidation.

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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
9.40%
发文量
218
审稿时长
6-12 weeks
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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