Mitochondrial Dysfunction in Type 2 Diabetes Mellitus: An Organ-Based Analysis.

Mitochondrial Dysfunction in Type 2 Diabetes Mellitus: An Organ-Based Analysis. Am J Physiol Endocrinol Metab. 2019 Jan 02;: Authors: Pinti MV, Fink GK, Hathaway QA, Durr AJ, Kunovac A, Hollander JM Abstract Type 2 diabetes mellitus (T2DM) is a systemic disease characterized by hyperglycemia, hyperlipidemia, and organismic insulin resistance. This pathologic shift in both circulating fuel levels and in 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, ß-cell insulin production, and neuronal health. While 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 progression such as mtDNA heteroplasmy, non-coding RNA (ncRNA), epigenetic modification of the mitochondrial genome, and epitranscriptomic regulation of the mtDNA-encoded mitoch...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research