Effects of imeglimin on experimental diabetic neuropathy in streptozotocin-induced diabetic rats
- J Diabetes Investig. 2026 Jun;17(6):951-960. doi: 10.1111/jdi.70303.
- 1. Laboratory of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Aichi, Japan.
- 2. Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
- 3. Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi, Japan.
- 4. Diabetic Neuropathy Project, Department of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
- 5. TDE Healthcare Corporation TOSAKI Meito Clinic for Diabetes and Endocrinology, Nagoya, Aichi, Japan.
- # Contributed equally.
Aims/introduction: As a common chronic complication, diabetic neuropathy affects a substantial number of individuals with diabetes mellitus, with limited therapeutic options addressing the underlying pathogenesis. The glucose-lowering action of imeglimin is mediated through improved Insulin sensitivity in peripheral organs, including the skeletal muscle and liver, along with augmented Insulin release from β-cells. Imeglimin exerts its effects in part by modulating mitochondrial complex I, leading to the reduced production of Reactive Oxygen Species and protection against metabolic stress. Despite these beneficial effects, the effect of imeglimin on diabetic neuropathy remains unclear. In this study, we evaluated whether imeglimin ameliorated peripheral nerve dysfunction in streptozotocin (STZ)-induced diabetic rats.
Materials and methods: The rats received imeglimin (200 mg/kg twice daily) or vehicle for 4 weeks, and the sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), sciatic nerve blood flow (SNBF), and intraepidermal nerve fiber density (IENFD) were assessed. Neurite outgrowth was examined in ND7/23 cells derived from the dorsal root ganglion.
Results: Imeglimin treatment significantly improved SNCV, SNBF, and IENFD without affecting blood glucose levels, indicating neuroprotective effects, independent of glycemic control. Furthermore, imeglimin enhanced neurite outgrowth in ND7/23 cells, demonstrating its direct neurotrophic effect. These findings indicate that imeglimin protects against diabetic neuropathy by enhancing nerve blood flow and promoting neurite growth independent of the systemic control of glycemia.
Conclusions: This study provides supporting evidence for the potential therapeutic application of imeglimin in diabetic neuropathy.