Imeglimin improves hyperglycemia and hypoglycemia-induced cell death and mitochondrial dysfunction in immortalized adult mouse Schwann IMS32 cells.

Aims/introduction: Imeglimin, a novel oral antidiabetic drug, enhances glucose-stimulated insulin secretion, improves insulin sensitivity, and reduces mitochondrial reactive oxygen species (ROS) generation. Diabetic neuropathy is driven by oxidative stress caused by hyperglycemia, with mitochondrial ROS overproduction playing a central role. Hypoglycemia also contributes to oxidative stress. This study evaluates the effects of imeglimin on Schwann cells under high- and low-glucose conditions.

Materials and methods: We used IMS32 cells, an immortalized mouse Schwann cell line, to investigate cell survival and mitochondrial function under normal, high-, and low-glucose conditions. Assessments included mitochondrial oxidative stress, cytochrome c release, mitochondrial membrane potential, oxygen consumption rate (OCR), Complex I activity, and ATP synthesis.

Results: High- and low-glucose conditions caused cell death, elevated mitochondrial ROS, triggered cytochrome c release, disrupted mitochondrial membrane potential, and increased OCR and Complex I activity, while suppressing ATP synthesis. Imeglimin treatment mitigated cell death, reduced oxidative stress, restored mitochondrial membrane potential, normalized OCR and Complex I activity, and improved ATP synthesis under both glucose conditions.

Conclusions: Fluctuations in glucose levels impair mitochondrial function in Schwann cells, contributing to peripheral nerve damage in diabetic neuropathy. Imeglimin demonstrated protective effects by alleviating mitochondrial dysfunction and preventing apoptosis signaling. These findings suggest the potential application of imeglimin in preventing and treating diabetic neuropathy; however, the clinical implications require further investigation.