The objective of this paper was to review the reported evidence concerning the mechanisms between lipid accumulation and insulin resistance. Lipid-induced insulin resistance in skeletal muscle is caused by defects in insulin-stimulated glucose transport activity. The steatotic liver in the context of insulin resistance is associated with an increase in hepatic glucose production. It is more and more recognized that ectopic accumulation of lipids within the muscle and the liver might be the consequence of insulin resistance. Several findings have suggested that impaired mitochondrial function with an impaired capacity to oxidize fatty acids predisposes muscle to intramyocellular fat accumulation. Moreover, intracellular accumulation of lipids (diacylglycerol) in muscle and liver triggers the activation of novel protein kinases C (PKCs) that interfere with insulin signalling and cause insulin resistance. In addition, the insulin sensitizing effects of weight loss and thiazolidinedione is induced by intracellular diacylglycerol content reduction. Thus, further studies are needed to improve our understanding of the activation of PKCs by diacylglycerol accumulation and the mechanism through which PKC impairs insulin signalling.
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