Ryan 2016 Diabetes
|Ryan TE, Schmidt CA, Green TD, Spangenburg EE, Neufer PD, McClung JM (2016) Targeted expression of catalase to mitochondria protects against ischemic myopathy in high fat fed mice. Diabetes 65:2553-68.|
Abstract: Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We sought to test whether diet induced mitochondrial dysfunction and oxidative stress would increase the susceptibility of the peripheral limb to hindlimb ischemia (HLI). Six weeks of high fat diet (HFD) in C57BL/6 mice was insufficient to alter skeletal muscle mitochondrial content and respiratory function or the size of ischemic lesion after HLI, despite reducing blood flow. However, sixteen weeks of HFD similarly decreased ischemic limb blood flow, but also exacerbated limb tissue necrosis, increased the myopathic lesion size, reduced muscle regeneration, attenuated muscle function, and exacerbated ischemic mitochondrial dysfunction. Mechanistically, mitochondrial targeted overexpression of catalase (MCAT) prevented the HFD-induced ischemic limb necrosis, myopathy, and mitochondrial dysfunction, despite no improvement in limb blood flow. These findings demonstrate that skeletal muscle mitochondria are a critical pathological link between type 2 diabetes and PAD. Furthermore, therapeutically targeting mitochondria and oxidant burden is an effective strategy to alleviate tissue loss and ischemic myopathy during PAD.
© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. • Keywords: Amplex Red
• O2k-Network Lab: US NC Greenville Neufer PD
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Diabetes Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Isolated mitochondria Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, CIV, Other combinations, ROX HRR: Oxygraph-2k