Glycemic Variability Affects Ischemia-Induced Angiogenesis In Diabetic MiceReport as inadecuate




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* Corresponding author 1 Internal Medicine

Abstract : The aim of this study was to investigate the role of glycemic variability GV on diabetic vascular complications and to explore the molecular pathways modulated by glycemic -swings-.We performed a murine model. 30 diabetic mice received once daily basal insulin administration plus 2 oral bolus of glucose solution GV group, V and 30 diabetic mice received once daily basal insulin plus 2 oral bolus of saline solution stable hyperglycemia group, S for a period of 30 days. Glycemia was measured 8 times daily to detect GV. Finally, post-ischemic vascularization, induced by hindlimb ischemia 30 days after diabetes onset, was evaluated.We found that GV was significantly different between S and V groups, whereas no significant difference of the mean glycemic values was detected. Laser Doppler perfusion imaging and histological analysis revealed that the ischemia-induced angiogenesis was significantly impaired in V mice compared to S group, after ischemic injury. In addition, immunostaining and western blot analyses revealed that impaired angiogenic response in V mice occurred in association with reduced VEGF production and decreased eNOS and Akt phosphorylation.In conclusion, we describe a murine model of GV. GV causes an impairment of ischemia-induced angiogenesis in diabetes, likely to be independent of changes in average blood glucose levels, and this impaired collateral vessel formation is associated with an alteration of the VEGF pathway.

keyword : Medicine





Author: Federico Biscetti - Dario Pitocco Giuseppe Straface Francesco Zaccardi Raimondo De Cristofaro Paola Rizzo Stefano Lancellotti Vin

Source: https://hal.archives-ouvertes.fr/



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