APOE and diabetes mellitus: TR4 knockout mice show insulin hypersensitivity [16] and TR4 can be induced by certain essential fatty acids resulting in TR4 activation followed by the up-regulation of the apolipoprotein E precursor (ApoE) and cytosolic phosphoenolpyruvate carboxykinase 1 PEPCK gene [30], which is thought to contribute to diabetics-induced hyperglycemia [40,41].