Ction compared with fasting at 0 min in controls (, n = 4) and bigenic (, n = 9). P 0.025 compared with 0 min. P 
0.004 comparing groups at 15 min. D : Isolated islets from 11-week-old bigenic mice (both CAIICre;Pdx1FlFl and CAIICre;Pdx1Fl+, , n = 10 animals) in sequential static incubation had impaired glucose-responsive insulin secretion compared with controls (, n = 10 animals) (D) and reduced percentage insulin content secreted (E) although the islet insulin content material was not considerably distinct (F). Data are imply 6 SEM. P 0.007. Even though each and every islet aliquot with values for each glucose concentrations (n = 23 for bigenic and n = 26 for control) was utilized for the averaging, the basal levels and islet insulin content material usually do not differ, however the bigenic islets showed a modest glucose-stimulated insulin release (2.6 mmolL glucose: 3.6 6 1.1 pg insulinng DNA; 16.eight mmolL glucose: 12.5 6 three.6 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21269526 pg insulinng DNA; P 0.003, paired t test).a section of CAIICre;Pdx1Fl pancreas, some islets (whether huge, small or as smaller clusters) could be identified containing cells with very low to undetectable PDX1 expression. Some islets had strongly homogeneous PDX1 staining, using a minority of cells displaying small or no PDX1 staining. The intensity of insulin staining also varied similarly. Therefore, there was a mixed population of islets in the CAIICre;Pdx1Fl3462 DIABETES, VOL. 62, OCTOBERmice (Fig. 5B): about 30 had homogeneously high or regular PDX1 expression, 20 had low to undetectable expression, and 50 displayed mixed-level expression. PDX1nullinsulin+ cells accounted for 31 6 7.7 of all insulin+ cells (n = 3 animals with at the very least 18 isletaggregates, and 625 insulin+ cells counted for each). The loss of PDX1 MK-0812 (Succinate) site expression was similarly seen inside the pancreas of 4-week-olddiabetes.diabetesjournals.orgL. GUO AND ASSOCIATESFIG. four. Duct-specific Pdx1-deficient mice had equivalent islet and b-cell mass as controls. Islet mass at four and ten weeks (A) and b-cell mass at 4 weeks (B) didn’t differ among handle () and CAIICre;Pdx1FlFl () male mice (4 weeks: n = 5 control, n = 6 bigenic; 10 weeks: n = 3 both groups). At four weeks the relative density of b-cells (C) differed, but due to the fact the pancreatic weights (D) have been enhanced inside the bigenic (despite the fact that they had comparable body weights) mice (E), the absolute b-cell mass was not lowered inside the bigenic mice. F: At four weeks, even though there was no difference in proliferation of acinar or duct (CK+) cells among handle and bigenic mice, proliferation in insulin+ cells was improved in each bigenic groups (G) compared with controls (H) with Ki67+ (red), PDX1 (green), and nuclei DAPI (blue). Data for individual animals are shown in F. I: Some Ki67+insulin+ (blue) cells have been PDX12. Information are mean 6 SEM. P 0.05.CAIICre;Pdx1FlFl (Supplementary Fig. 4) and of CAIICre; Pdx1Fl+ mice at each ages (data not shown). When the ROSA26ReYFP reporter gene was introduced into the CAIICre; Pdx1 mice for lineage tracing, some lobes had YFP+ acinar and islet cells (Fig. 6A and Supplementary Fig. 5). These YFP islets have some b-cells with low to undetectable PDX1 expression, and other folks cells had powerful PDX1 expression. In islets of 10- to 12-week-old mice, the b-cell transcription factor MAFA had a similarly mixed expression pattern to that of PDX1. Within the identical section, some islets on the bigenic mice had small to no MAFA protein expression, within a extremely heterogeneous pattern, whereas other folks had expression indistinguishable from controls (F.