Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids.

Diabetes Metab Res Rev 2015 Jul 18;31(5):453-75. Epub 2014 Oct 18.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid-induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation-induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes.

Download full-text PDF

Source
http://dx.doi.org/10.1002/dmrr.2601DOI Listing
July 2015
140 Reads
10 Citations

Publication Analysis

Top Keywords

insulin resistance
24
type diabetes
12
long chain
8
resistance type
8
oxidative stress
8
chain fatty
8
mitochondrial dysfunction
8
insulin
7
resistance
6
target tissues
4
tissues skeletal
4
skeletal muscle
4
metabolism target
4
oxidative metabolism
4
resistance alteration
4
alteration oxidative
4
experimental studies
4
liver adipose
4
review propose
4
propose idea
4

Similar Publications