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 (each 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 reduce percentage insulin content material secreted (E) despite the fact that the islet insulin content was not significantly different (F). Information are mean 6 SEM. P 0.007. Even when each and every islet aliquot with values for both glucose concentrations (n = 23 for bigenic and n = 26 for handle) was employed for the averaging, the basal levels and islet insulin content do not differ, but the bigenic islets showed a modest glucose-stimulated insulin release (2.6 mmolL glucose: 3.six six 1.1 pg insulinng DNA; 16.8 mmolL glucose: 12.five six 3.six 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 (regardless of whether substantial, small or as smaller clusters) could be found containing cells with very low to undetectable PDX1 expression. Some islets had strongly homogeneous PDX1 staining, having a minority of cells displaying little or no PDX1 staining. The intensity of insulin staining also varied similarly. Hence, there was a mixed population of islets within the CAIICre;Pdx1Fl3462 DIABETES, VOL. 62, OCTOBERmice (Fig. 5B): about 30 had homogeneously higher or typical PDX1 expression, 20 had low to undetectable expression, and 50 displayed mixed-level expression. PDX1nullinsulin+ cells accounted for 31 six 7.7 of all insulin+ cells (n = three animals with a minimum of 18 isletaggregates, and 625 insulin+ cells counted for each). The loss of PDX1 expression was similarly noticed inside the pancreas of 4-week-olddiabetes.diabetesjournals.orgL. GUO AND ASSOCIATESFIG. four. Duct-specific Pdx1-deficient mice had comparable islet and b-cell mass as controls. Islet mass at four and ten weeks (A) and b-cell mass at four weeks (B) did not differ among handle () and CAIICre;Pdx1FlFl () male mice (4 weeks: n = five manage, n = 6 bigenic; 10 weeks: n = 3 both groups). At 4 weeks the relative density of b-cells (C) differed, but because the pancreatic weights (D) were enhanced in the bigenic (even though they had comparable body weights) mice (E), the absolute b-cell mass was not decreased in the bigenic mice. F: At four weeks, even though there was no distinction in Gynostemma Extract web proliferation of acinar or duct (CK+) cells amongst manage and bigenic mice, proliferation in insulin+ cells was elevated in each bigenic groups (G) compared with controls (H) with Ki67+ (red), PDX1 (green), and nuclei DAPI (blue). Information for individual animals are shown in F. I: Some Ki67+insulin+ (blue) cells had 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 in to 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 people cells had strong PDX1 expression. In islets of 10- to 12-week-old mice, the b-cell transcription aspect MAFA had a similarly mixed expression pattern to that of PDX1. Within exactly the same section, some islets with the bigenic mice had small to no MAFA protein expression, inside a extremely heterogeneous pattern, whereas other individuals had expression indistinguishable from controls (F.
