Obesity and lipid oversupply have been linked with defective insulin action in liver and muscle for some time. As lipid-activated kinases, isoforms of the protein kinase C (PKC) family are strong candidates for mediating the inhibitory effects of lipid intermediates. More specifically, PKCĪµ is widely believed to play a direct role in liver insulin resistance through inhibition of proximal insulin signalling. Our laboratory has extensively investigated the effects of global and tissue-specific PKCĪµ ablation on in mice. This has revealed previously unsuspected roles for the kinase in the regulation of lipid metabolism and glucose homeostasis.