Sirt1-deficient islets present impaired glucose-stimulated insulin secretion but no changes in insulin positive islet area or islet size.

<p>A. Sirt1 transcript levels analyzed by RT-qPCR in isolated islets of Pdx1^Cre and Pdx1^Cre; Sirt1^ex4F/F mice. Values are relative to the housekeeping gene. (<i>n</i>≥6, ****<i>p</i><0.0001). B. Percentage of islet distribution according to size as measured by morphometry in pancreata from Pdx1^Cre; Sirt1^ex4F/F and control mice. (<i>n =</i> 6). C. Relative insulin positive area over total pancreas area in Pdx1^Cre; Sirt1^ex4F/F and control mice as analyzed by morphometry. (<i>n =</i> 6). D. <i>Ex vivo</i> insulin secretion in islets isolated from 6-month-old Pdx1^Cre and Pdx1^Cre; Sirt1^ex4F/F male animals. Batches of five islets were incubated in HEPES-buffered KRB containing 0.1% BSA and 2 mmol/L (G2) or 20 mmol/L glucose (G20) for 1 h. Insulin release was determined by RIA. (<i>n</i> = 5–7, *<i>p</i><0.05, ***<i>p</i><0.001 for the effect of glucose, # <i>p</i><0.05 for the effect of genotype).