Figure 2.

An illustration of how mitochondrial impairments can lead to a decrease in insulin sensitivity. Mitochondrial toxicity can lead to a decrease in the metabolism of lipids leading to the accumulation of ceramides and diacylglycerol which lead into the impairment of the insulin signalling pathway. The elevation of these metabolites can lead to a disruption of the insulin signalling pathway through the activation of stress-sensitive kinases such as PKC, ikappaB kinase IKK, and JNK. These stress-sensitive kinases can phosphorylate and inactivate IRS1 and IRS2.