Zabielski 2016 Diabetes

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Zabielski P, Lanza IR, Gopala S, Holtz Heppelmann CJ, Bergen HR 3rd, Dasari S, Nair KS (2016) Altered skeletal muscle mitochondrial proteome as the basis of disruption of mitochondrial function in diabetic mice. Diabetes 65:561-73.

» PMID: 26718503

Zabielski P, Lanza IR, Gopala S, Holtz Heppelmann CJ, Bergen HR 3rd, Dasari S, Nair KS (2016) Diabetes

Abstract: Insulin plays pivotal role in cellular fuel metabolism in skeletal muscle. Despite being the primary site of energy metabolism, the underlying mechanism on how insulin deficiency deranges skeletal muscle mitochondrial physiology remains to be fully understood. Here we report an important link between altered skeletal muscle proteome homeostasis and mitochondrial physiology during insulin deficiency. Deprivation of insulin in streptozotocin-induced diabetic mice decreased mitochondrial ATP production, reduced coupling and phosphorylation efficiency, and increased oxidant emission in skeletal muscle. Proteomic survey revealed that the mitochondrial derangements during insulin deficiency were related to increased mitochondrial protein degradation and decreased protein synthesis, resulting in reduced abundance of proteins involved in mitochondrial respiration and β-oxidation. However, a paradoxical upregulation of proteins involved in cellular uptake of fatty acids triggered an accumulation of incomplete fatty acid oxidation products in skeletal muscle. These data implicate a mismatch of β-oxidation and fatty acid uptake as a mechanism leading to increased oxidative stress in diabetes. This notion was supported by elevated oxidative stress in cultured myotubes exposed to palmitate in the presence of a β-oxidation inhibitor. Together, these results indicate that insulin deficiency alters the balance of proteins involved in fatty acid transport and oxidation in skeletal muscle, leading to impaired mitochondrial function and increased oxidative stress.

© 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: C2C12 mouse myoblast, Myotubes

O2k-Network Lab: US MN Rochester Nair KS, IN Thiruvananthapuram Gopala S


Labels: MiParea: Respiration  Pathology: Diabetes  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

2016-05