Figure 2. Insulin resistance-induced β cell de-differentiation is reversible.
(A) Immunostaining with antibodies against insulin (red) and Ucn3 (green) in pancreata from wild-type C57BL/6 mice treated with either vehicle (PBS) or S961 (insulin receptor antagonist) for 7 days (upper and middle panels) or treated with S961 for 7 days followed by a 7-day-recovery period in the absence of S961 (lower panel). Ucn3 protein expression is down regulated in β cells following 7 days S961 treatment but returns to normal expression levels upon remission to normoglycaemia (see text). Nuclei are stained with DAPI (blue). (B) Quantitative Real-Time PCR analysis of Ins1 and Ucn3 gene expression in islets from ICR lean mice taken at different time points during S961-induced de-differentiation and post S961 withdrawal recovery (n = 3 mice for each stage). S961 osmotic pumps are transplanted on day 0 and removed on day 7. Control designates mice not treated with S961. Error bars represent ±SEM. *p < 0.05; ***p < 0.005.