Pancreatic and duodenal homeobox-1 nuclear localization is regulated by glucose in dispersed rat islets but not in insulin-secreting cell lines

摘要

The transcription factor Pancreatic and Duodenal Homeobox-1 (PDX-1) plays a major role in the development and function of pancreatic beta-cells and its mutation results in diabetes. In adult beta-cells, glucose stimulates transcription of the insulin gene in part by regulating PDX-1 expression, stability and activity. Glucose is also thought to modulate PDX-1 nuclear translocation but in vitro studies examining nucleo-cytoplasmic shuttling of endogenous or ectopically expressed PDX-1 in insulin-secreting cell lines have led to conflicting results. Here we show that endogenous PDX-1 undergoes translocation from the cytoplasm to the nucleus in response to glucose in dispersed rat islets but not in insulin-secreting MIN6, HIT-T15, or INS832/13 cells. Interestingly, however, we found that a PDX-1-GFP fusion protein can shuttle from the cytoplasm to the nucleus in response to glucose stimulation in HIT-T15 cells. Our results suggest that the regulation of endogenous PDX-1 sub-cellular localization by glucose is observed in primary islets and that care should be taken when interpreting data from insulin-secreting cell lines.