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      Platelet Mitochondrial Dysfunction is Evident in Type 2 Diabetes in Association with Modifications of Mitochondrial Anti-Oxidant Stress Proteins

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          Abstract

          Objective:

          Mitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells.

          Method:

          A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive ( n=8) and type 2 diabetic subjects ( n=7).

          Results:

          In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic versus control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls.

          Conclusions:

          As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This ‘stress-signature’ in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as “accessible human tissue”, may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.

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          Author and article information

          Journal
          9505926
          8744
          Exp Clin Endocrinol Diabetes
          Exp. Clin. Endocrinol. Diabetes
          Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
          0947-7349
          1439-3646
          23 August 2018
          15 September 2011
          April 2012
          04 September 2018
          : 120
          : 4
          : 248-251
          Affiliations
          [1 ]Center for Molecular Medicine
          [2 ]Proteomics Core Facility, NHLBI, NIH, Bethesda, MD
          Author notes
          Address for correspondence: Michael N. Sack, MD, Ph.D., Center for Molecular Medicine, NHLBI, Building 10-CRC, Room 5-3150, 10 Center Drive, Bethesda, MD, 20892-1454, sackm@ 123456nhlbi.nih.gov
          Article
          PMC6122851 PMC6122851 6122851 nihpa986178
          10.1055/s-0031-1285833
          6122851
          21922457
          Categories
          Article

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