Imeglimin is a drug for type 2 diabetes that promotes β-cell proliferation; however, the detailed underlying molecular mechanism remains unclear. We investigated metabolites in pancreatic islets after imeglimin treatment via liquid chromatography with tandem mass spectrometry (LC–MS). Treatment with imeglimin for 24 hours increased adenylosuccinate (S-AMP), produced by adenylosuccinate synthase (ADSS) from inosine monophosphate (IMP) and aspartate in mouse islets. The levels of IMP and aspartate and both the mRNA and protein levels of adenylosuccinate synthase (Adss) were elevated following imeglimin treatment in islets. Alanosine, an inhibitor of ADSS, suppressed imeglimin-induced β-cell proliferation in mouse islets, human islets, human pluripotent stem cell-derived β-like cells, and porcine islets. These data suggested that treatment with imeglimin promotes β-cell proliferation partly through an increase in S-AMP production.

・Diabetes
・2025/7/10
・Adenylosuccinate mediates imeglimin-induced proliferative and antiapoptotic effects in β-cells.

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