There is some evidence that the two rodent insulin genes are differentially regulated in mice, although there is no satisfactory consensus on the relative levels and patterns of expression for the two genes. Using the mouse insulinoma cell line MIN6, we have demonstrated by quantitative RT-PCR, differential patterns of expression for the two genes. In mouse islets and early passage MIN6 cells, expression of ins I and ins 2 were found to be approximately equal, but levels of ins I mRNA diminished rapidly with continued passage. Furthermore, the ins I gene was found to be up-regulated in response to glucose stimulation and as a result of increased cell-cell contact, but no effect on the ins 2 gene was observed. Since the MIN6 cell line is frequently used as a P-cell model for gene expression studies, consideration should be given to both insulin genes. (C) 2002 Elsevier Science (USA). All rights reserved.