Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice.
Glucagon
Glucagon‐like peptide‐1
Imeglimin
Journal
Journal of diabetes investigation
ISSN: 2040-1124
Titre abrégé: J Diabetes Investig
Pays: Japan
ID NLM: 101520702
Informations de publication
Date de publication:
14 Jun 2024
14 Jun 2024
Historique:
revised:
03
05
2024
received:
03
01
2024
accepted:
24
05
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
14
6
2024
Statut:
aheadofprint
Résumé
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. 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. 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. 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Sumitomo Pharma Co., Ltd.
ID : BC10200001
Informations de copyright
© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
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