The role of mitochondria in the aetiology of insulin resistance and type 2 diabetes

• Published in: Biochimica et biophysica acta Vol. 1840; no. 4; pp. 1303 - 1312
• Main Authors: Martin, Sheree D., McGee, Sean L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2014
• Subjects: Animals; Apoptosis - physiology; Calcium Signaling - physiology; Diabetes Mellitus, Type 2 - etiology; Energy Metabolism - physiology; Humans; Inflammation; Insulin - physiology; Insulin Resistance; Lipid accumulation; Mitochondria - physiology; Mitochondrial dysfunction; Reactive oxygen species; Type 2 diabetes; Myo1c; Type 2 diabetes; TNFα; Reactive oxygen species; mtDNA; JNK; PTEN; PTP; Cox6a2; NPY; Tfam; AgRP; AIF; Mitochondrial dysfunction; PEPCK; NCLX; PGC-1α; Inflammation; POMC; MMP; CaMKII; TCA; G6Pase; ETC; Nox; ROS; AMPK; TXNIP; Insulin resistance; Lipid accumulation; MPTP; GLUT4; MICU1; CPT-1
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.09.019

The prevalence of type 2 diabetes is rapidly increasing world-wide and insulin resistance is central to the aetiology of this disease. The biology underpinning the development of insulin resistance is not completely understood and the role of impaired mitochondrial function in the development of insulin resistance is controversial.
This review will provide an overview of the major processes regulated by mitochondria, before examining the evidence that has investigated the relationship between mitochondrial function and insulin action. Further considerations aimed at clarifying some controversies surrounding this issue will also be proposed.
Controversy on this issue is fuelled by our lack of understanding of some of the basic biological interactions between mitochondria and insulin regulated processes in the context of insults thought to induce insulin resistance. Aspects that have not yet been considered are tissue/cell type specific responses, mitochondrial responses to site-specific impairments in mitochondrial function and as yet uncharacterised retrograde signalling from mitochondria.
Further investigation of the relationship between mitochondria and insulin action could reveal novel mechanisms contributing to insulin resistance in specific patient subsets. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.
•The role of mitochondrial (dys)function in insulin resistance is controversial.•A lack of understanding of the biology between mitochondria and insulin action exists.•Improved understanding of this relationship could reveal novel mechanisms of insulin resistance.