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


METHODS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Metabolic Remodelling Laboratory, Metabolic Research Unit, School of Medicine, Deakin University, Waurn Ponds 3217, Australia.
Sheree D
SD
Martin
Metabolic Remodelling Laboratory, Metabolic Research Unit, School of Medicine, Deakin University, Waurn Ponds 3217, Australia. Electronic address: sean.mcgee@deakin.edu.au.
Sean L
SL
McGee
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D008928:Mitochondria / Q000502:physiology*
D007328:Insulin
Inflammation; Insulin resistance; Lipid accumulation; Mitochondrial dysfunction; Reactive oxygen species; Type 2 diabetes