Figure 1.

Prox1 upregulation does not affect mature β-cell function. Prox1 (red) was expressed at very low levels in insulin⁺ cells (blue, arrowheads) and at high levels in glucagon⁺ cells (green, arrows) in the pancreata of wild-type mouse embryos (A), newborns (B), and adults (C). Asterisks indicate Prox1 expression in the pancreatic ducts. C′: Compared with Prox1, Pdx1 (red) levels were noticeably higher in insulin⁺ pancreatic cells (blue). C and C′ are consecutive sections. D: RIP-Cre–mediated excision of a GFP-STOP cassette in the Jojo-Prox1 transgene activated the expression of exogenous Prox1 and the β-gal reporter in β-cells of Prox1^betaOE mice. E: Very few cells expressed the β-gal reporter (blue, arrow) and high Prox1 (red) in Prox1^betaOE pancreata at P2. GFP expression (green) denoting lack of Cre activity was very extensive in the islet core (yellow arrow) at this stage. E′: Numerous cells expressed high Prox1 (red, arrow) and β-gal (blue) throughout the islet core in Prox1^betaOE adult pancreata. The arrowhead indicates Prox1 normal expression in peripheral islet cells. Both the blood glucose levels under fed (fast and fed [F&F]) and fasting (Fast) conditions (F) and the glucose clearance response (G) were comparable between Prox1^betaOE and control mice (RIP-Cre). The expression of Pdx1 (red [H and H′]), GLUT2 (red [I and I′]), and MafA (red [J and J′]) in insulin⁺ cells (blue) was indistinguishable between control (RIP-Cre [H–J]) and Prox1^betaOE (H′–J′) adult pancreata. A–C and C′ are confocal images. G: Error bars represent +SEM values; n = 5–6 mice per genotype. Scale bars: 25 μm.