A 14.5-kb pdx1 genomic fragment corrected the glucose intolerance of pdx1(+/-) animals but, moreover, fully rescued the severe gut and pancreas defects in pdx1(-/-) embryos.
Adult Tshz1(+/-) mice display glucose intolerance due to defects in glucose-stimulated insulin secretion associated with reduced Pdx1 and Clec16a expression in Tshz1(+/-) islets.
Mice that are haploinsufficient for Pdx1 display impaired glucose tolerance and lack the ability to increase beta cell mass in response to decreased insulin signaling.
We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance.
Heterozygous mutations in the gene result in impaired glucose tolerance and symptoms of diabetes as seen in MODY4 and late-onset Type II (non-insulin-dependent) diabetes mellitus.
<i>Plcb1</i><sup>f/f</sup>; <i>Pdx1-CreERt2</i> mice fed a high-fat diet developed more severe glucose intolerance because of a defect in insulin secretion.