Diabetes Worsens Skeletal Muscle Mitochondrial Function, Oxidative Stress, and Apoptosis After Lower-Limb Ischemia-Reperfusion: Implication of the RISK and SAFE Pathways?

Fiche publication

Date publication

janvier 2018

Journal

Frontiers in physiology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel , Dr LAVERNY Gilles , Pr GENY Bernard

Tous les auteurs :
Pottecher J, Adamopoulos C, Lejay A, Bouitbir J, Charles AL, Meyer A, Singer M, Wolff V, Diemunsch P, Laverny G, Metzger D, Geny B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29872405

Résumé

Diabetic patients respond poorly to revascularization for peripheral arterial disease (PAD) but the underlying mechanisms are not well understood. We aimed to determine whether diabetes worsens ischemia-reperfusion (IR)-induced muscle dysfunction and the involvement of endogenous protective kinases in this process. Streptozotocin-induced diabetic and non-diabetic rats were randomized to control or to IR injury (3 h of aortic cross-clamping and 2 h of reperfusion). Mitochondrial respiration, reactive oxygen species (ROS) production, protein levels of superoxide dismutase (SOD2) and endogenous protective kinases (RISK and SAFE pathways) were investigated in rat gastrocnemius, together with upstream (GSK-3β) and downstream (cleaved caspase-3) effectors of apoptosis. Although already impaired when compared to non-diabetic controls at baseline, the decline in mitochondrial respiration after IR was more severe in diabetic rats. In diabetic animals, IR-triggered oxidative stress (increased ROS production and reduced SOD2 levels) and effectors of apoptosis (reduced GSK-3β inactivation and higher cleaved caspase-3 levels) were increased to a higher level than in the non-diabetics. IR had no effect on the RISK pathway in non-diabetics and diabetic rats, but increased STAT 3 only in the latter. Type 1 diabetes worsens IR-induced skeletal muscle injury, endogenous protective pathways not being efficiently stimulated.