M Lachaux, M Souli
INSERM U1096, UFR de Sant
Endochrinology, Diabetes and Metabolism
IntroductionImeglimin, a glucose_lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome_related left ventricular (LV) and vascular dysfunctions.
Methods We used Zucker fa/fa rats to assess the effects on LV function, LV tissue perfusion, LV oxidative stress and vascular function induced by imeglimin administered orally for 9 or 90 days at a dose of 150 mg/kg twice daily.
Results Compared to untreated animals, 9_ and 90_day imeglimin treatment decreased LV end_diastolic pressure and LV end_diastolic pressure_volume relation, increased LV tissue perfusion and decreased LV ROS production. Simultaneously, imeglimin restored acetylcholine_mediated coronary relaxation and mesenteric flow_mediated dilation. One hour after imeglimin administration, when glucose plasma levels were not yet modified, imeglimin reduced LV mitochondrial ROS production and improved LV function. Ninety_day imeglimin treatment reduced related LV and kidney fibrosis and improved kidney function.
Conclusion In a rat model, mimicking Human metabolic syndrome, imeglimin immediately countered metabolic syndrome_related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion and after 90_day treatment myocardial and kidney structure, effects that are, at least in part, independent from glucose control.
BIOSEB Instruments Used:
Treadmill (BX-TM),Passive avoidance (LE870)