Imeglimin Protects β-Cells from Apoptosis via ER Homeostasis Pathway

What is it about?

In a study on the effects of imeglimin, a new antidiabetes agent, on b-cell function, it was found that imeglimin enhanced glucose-induced insulin secretion, increased b-cell proliferation, and prevented b-cell apoptosis in a glucose-dependent manner. Imeglimin modulated the ER homeostasis pathway, including negative feedback of the CHOP/GADD34 pathway, ATF3, or SDF2L1-mediated signaling, to prevent β-cell apoptosis. Imeglimin upregulated complex I protein, which establishes the hydrogen ion gradient by pumping hydrogen ions into the intermembrane space, and increased ATP production, mitochondrial basal respiration, and maximal respiration under high-glucose conditions in isolated islets. Additionally, imeglimin tended to increase Ern1 mRNA expression under high-glucose conditions. The pathway analysis indicated that imeglimin possibly regulates the MAPK/EGFR1/G-protein-coupled receptor signaling pathway.

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Why is it important?

This research is important because it provides insights into the effects of imeglimin, a novel antidiabetes agent, on β-cell function and its impact on the prevention of β-cell apoptosis. It demonstrates that imeglimin modulates the ER homeostasis pathway, which ultimately results in the prevention of β-cell apoptosis both in vitro and in vivo. This finding could potentially lead to the development of new therapeutic strategies for the treatment of diabetes. Key Takeaways: 1. Imeglimin enhances glucose-induced insulin secretion, increases β-cell proliferation, and prevents β-cell apoptosis in a glucose-dependent manner. 2. Imeglimin prevents ER stress-mediated b-cell apoptosis, at least in part, through the modulation of ER homeostasis, including negative feedback of the CHOP/GADD34 pathway, ATF3, or SDF2L1-mediated signaling. 3. Imeglimin upregulates complex I protein, increases ATP production, mitochondrial basal respiration, and maximal respiration under high-glucose conditions, which may improve mitochondrial function and increase ATP production under high-glucose conditions in isolated islets.