Pdx1^Cre; Sirt1^ex4F/F islets have impaired expression of Endoplasmic Reticulum (ER) chaperone genes involved in the Unfolded Protein Response (UPR) pathway.

<p>A. Pathway enrichment analysis of genes differentially expressed in Pdx1^Cre vs Pdx1^Cre;Sirt1^ex4F/F whole pancreata. (<i>n</i> = 3, p<0.001). B. UPR pathway gene transcript levels analyzed by RT-qPCR in Pdx1^Cre and Pdx1^Cre; Sirt1^ex4F/F isolated islets. Values are relative to the housekeeping gene. (<i>n</i>≥6, **<i>p</i><0.01). C. <i>Xbp1</i> Splicing. <i>Xbp1</i> cDNA was amplified by PCR and digested with <i>PstI</i>. Spliced <i>Xbp1</i> lacks the restriction site and remains intact. Spliced (intact) and unspliced (cut) <i>Xbp1</i> were quantified by densitometry. The value obtained for spliced <i>Xbp1</i> was expressed as a ratio of the total (spliced + unspliced) <i>Xbp1</i> mRNA level for each sample. (<i>n</i>≥6). D. Immunofluorescence staining of Insulin and Bip/Hspa5 and Grp94/Hsp90b1 (anti-KDEL antibody) in islets of Pdx1^Cre and Pdx1^Cre; Sirt1^ex4F/F animals. Nuclei are counterstained with DAPI. A representative picture is shown.