Clearance of apoptotic β-cells is reduced in neonatal autoimmune diabetes-prone rats

Abstract

The kinetics of β-cell death in neonatal diabetes-prone (BBdp) and diabetes-resistant (BBdr) BioBreeding rats was investigated using both direct (histochemical) and indirect (mathematical modelling) techniques. In both BBdp and BBdr rats, the incidence of TUNEL positive β-cells increased until 10 days of age before declining. The number of apoptotic β-cells was significantly higher in BBdp as compared to BBdr neonates from birth until 20 days of age (Pin vitro phagocytosis of apoptotic thymocytes by peritoneal macrophages from 2-week-old BBdp and BBdr rats. Macrophages from BBdp neonates engulfed significantly less apoptotic cells as compared to BBdr neonates (P<0.0005). Taken together, these findings suggest that there is impaired clearance of apoptotic β-cells in diabetes-prone BB rats during the neonatal period.