LAUSR

Imeglimin (IME) is a novel glucose-lowering agent improving insulin secretion in response to glucose and insulin sensitivity by targeting mitochondrial bioenergetics. IME is currently in phase 3 in Japan. The toxicity of high glucose or fructose concentrations in INS-1 cells was linked to the opening of the permeability transition pore (PTP), a mitochondrial channel involved in cell death. IME has been shown to prevent PTP opening in human endothelial cells under oxidative stress. This study investigated whether IME could also prevent PTP opening and cell death induced by high glucose or fructose concentrations in INS-1 cells and human pancreatic islets. PTP status in intact cells was assessed by confocal microscopy by measuring mitochondrial membrane potential (TMRM) and NAD(P)H (autofluorescence). Cell viability was measured by flow cytometry. In INS-1 cells and human islets, 30 mM Glucose or 2.5 mM Fructose for 24h led to PTP opening (increase in the NAD(P)H/TMRM ratio), this phenomenon being prevented by 100µM IME. Compared to normal glucose concentration (100%), cell viability significantly decreased (p Disclosure S. Lablanche: Other Relationship; Self; Poxel SA. E. Tubbs: None. C. Cottet-Rousselle: None. F. Lamarche: None. A. Moisan: None. V. Persoons: None. P.Y. Benhamou: Consultant; Self; Abbott, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Eli Lilly and Company, Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Diabeloop S.A.. S. Hallakou-Bozec: None. E. Fontaine: Other Relationship; Self; Poxel SA.