Reduced IDX-1 can lead to type 2 diabetes

The homeodomain transcription factor IDX-1 is a critical regulator of pancreatic development and insulin gene transcription. In the absence of these processes there is a strong predisposition to the development of diabetes mellitus in humans. In July Journal of Clinical Investigation, Melissa Thomas and colleagues from Harvard Medical School, Boston, Massachusetts show that a reduction of IDX-1 levels in pancreatic β cells in combination with aging is enough to induce metabolic dysfunction and type 2 (non-insulin dependent) diabetes.

Thomas et al. developed a model for the inducible impairment of in vivo IDX-1 expression in β cells by engineering an antisense ribozyme specific for murine IDX-1 mRNA under control of the reverse tetracycline transactivator (rtTA). Doxycycline-induced impairment of IDX-1 expression activated the Idx-1 promoter and was followed by elevated glycated haemoglobin levels and diminished glucose tolerance. In addition, metabolic phenotypes induced by IDX-1 deficiency were observed predominantly in male mice over ...