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Mitochondrial Dysfunction In Type 2 Diabetes Mellitus: An Organ-based Analysis.
M. Pinti, Garrett K. Fink, Q. A. Hathaway, Andrya J. Durr, Amina Kunovac, J. Hollander
Published 2019 · Medicine
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Type 2 diabetes mellitus (T2DM) is a systemic disease characterized by hyperglycemia, hyperlipidemia, and organismic insulin resistance. This pathological shift in both circulating fuel levels and energy substrate utilization by central and peripheral tissues contributes to mitochondrial dysfunction across organ systems. The mitochondrion lies at the intersection of critical cellular pathways such as energy substrate metabolism, reactive oxygen species (ROS) generation, and apoptosis. It is the disequilibrium of these processes in T2DM that results in downstream deficits in vital functions, including hepatocyte metabolism, cardiac output, skeletal muscle contraction, β-cell insulin production, and neuronal health. Although mitochondria are known to be susceptible to a variety of genetic and environmental insults, the accumulation of mitochondrial DNA (mtDNA) mutations and mtDNA copy number depletion is helping to explain the prevalence of mitochondrial-related diseases such as T2DM. Recent work has uncovered novel mitochondrial biology implicated in disease progressions such as mtDNA heteroplasmy, noncoding RNA (ncRNA), epigenetic modification of the mitochondrial genome, and epitranscriptomic regulation of the mtDNA-encoded mitochondrial transcriptome. The goal of this review is to highlight mitochondrial dysfunction observed throughout major organ systems in the context of T2DM and to present new ideas for future research directions based on novel experimental and technological innovations in mitochondrial biology. Finally, the field of mitochondria-targeted therapeutics is discussed, with an emphasis on novel therapeutic strategies to restore mitochondrial homeostasis in the setting of T2DM.
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Insulinemic Potential of Lifestyle Is Inversely Associated with Leukocyte Mitochondrial DNA Copy Number in US White Adults.
Keming Yang (2020)
Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone
A. Diané (2020)
Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1α Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species
D. Kim (2020)
Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes
Kanwal Rehman (2020)
Myocardial glucotoxicity: Mechanisms and potential therapeutic targets.
S. Battault (2020)
The balancing act of NEET proteins: Iron, ROS, calcium and metabolism.
R. Nechushtai (2020)
Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm
Jacob Bar-Tana (2020)
Amyloid Proteins and Peripheral Neuropathy
Mohammed M H Asiri (2020)See more