FIGURE 1.
Aged rat islets are refractory to mitogenic signals that induce proliferation in young rat islets. (A) Young (5 week) and aged (5 month) islets (n = 6 each) were left untransduced or transduced with AdCMV-GFP, AdCMV-Nkx6.1, AdCMV-Pdx1, AdCMV-Nr4a1, AdCMV-Nr4a3, or AdCMV-Cyclin D1. Young islets demonstrated increased proliferation as measured by 3H-thymidine incorporation, while aged islets had impaired proliferation (n = 6 mice per age). Young and aged islets (n = 4 mice per age) express (B) Nkx6.1 and (C) GFP mRNA levels at similar levels after adenoviral transduction. (D) Young and aged rats have equal sized islets, apart from islets with a size of 6300 μM2 being more prevalent in aged pancreata (n = 5 mice per age). (E) No difference in percent Insulin positive area between young and aged pancreata (n = 4 mice per age). (F) Entry points of tested mitogenic signals to the cell cycle, and general locations of influence of cyclin dependent kinase inhibitors. ****p < 0.0001