Abstract
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and the metabolic syndrome. In this lecture I will discuss recent nuclear magnetic resonance studies that have implicated ectopic lipid deposition in liver and skeletal muscle as a causal and unifying factor in the pathogenesis of insulin resistance associated with obesity, lipodystrophy, type 2 diabetes and the metabolic syndrome. I will also present results from recent human studies demonstrating an important role of intracellular diacylglycerol, as the molecular trigger for lipid-induced insulin resistance in liver through its activation of protein kinase Ce and in muscle through its activation of protein kinase Cθ, which both result in reductions in proximal insulin signaling.
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