Sox17-paLOF mice develop high fat diet-induced β cell dysfunction and lose β cell mass.

<p><b>A)</b> Over the course of 23 weeks on a high fat diet, there was no difference in weight gain between Control (Pdx1Cre;Sox17^fl/+, n = 3) and Sox17-paLOF (Pdx1Cre;Sox17^fl/fl, n = 4–6) littermates. <b>B)</b> Food intake measurements showed no difference between genotypes. <b>C)</b> Analysis of fasting blood glucose levels. Sox17-paLOF had higher fasting glucose levels than control mice. Asterisk show p-value≤0.01. <b>D)</b> Glucose tolerance test showed impaired glucose clearance in the Sox17-paLOF mice 21 weeks after high fat diet administration. The asterisks indicate p-value≤0.05. <b>E)</b> Impact of Sox17-paLOF on islets. Pancreatic sections (n = 2 mice per genotype, 6 whole pancreatic sections analyzed per mouse) from each animal were stained with insulin, Pdx1, and Dapi and indicated significant reduction in islet size in Sox17-paLOF mice. Scale bar: 2000 µm. <b>F)</b> Islet organization is disrupted in Sox17-paLOF mice. Insulin, Pdx1, and glucagon staining showed loss of β cell mass and a prevalence of alpha cells in the islet core of Sox17-paLOF mice. Scale bar: 30,000 µm <b>G)</b> Quantification of loss of islet mass in Sox17-paLOF mice. The islet and total pancreas surface areas were calculated using Imaris Software. (n = 2 mice per genotype, 6 whole pancreatic sections analyzed per mouse).