Resistance to hormone action is often explained by alterations in hormone receptors, transduction mechanisms or enzymes. Two recent reports suggest that, in the case of insulin resistance, alterations in gene expression control at the nuclear level (in particular, transcriptional regulation) might also represent a potential mechanism for resistance to hormone action in human disease. The transcriptional regulation of gene expression is controlled by regulatory proteins known as transcription factors (or trans-acting factors). They bind to defined DNA sequences in the regulatory regions of specific genes (cis-elements). It was tempting to speculate that alteration in trans-acting factors or ciselements implicated in insulin action could result in insulin resistance.
Apolipoprotein C-III (apo C-III) is present in triglyceride-rich lipoproteins. In diabetic mice, a clear increase in apo C-III is observed. Transcription of the apo C-III gene is inhibited by insulin. Several observations suggest that apo C-III overexpression might be