Apoptosis and occurrence of Bcl-2, Bak, Bax, Fas and FasL in the developing and adult rat endocrine pancreas

Apoptotic cell death is thought to play a crucial role in the manifestation of insulin- and non-insulin dependent diabetes mellitus. Therefore, apopto sis and apoptotic markers were studied in the rat endocrine pancreas to get insight into the possible life cycle of Langerhans islets. The islets were investigated at 13 time points between day E19 and is months. At each time point, histologic sections were treated with the direct fluorescein-labell ed TUNEL method and immunostained for pancreatic hormones (glucagon, insuli n), apoptotic promoters (Bak, Bar, Fas, Fas Ligand) as well as for the anti -apoptotic peptide Bcl-2. All tissue sections were investigated using confo cal laser scanning microscopy under identical settings for semiquantitative estimation of staining intensity. TUNEL-positive cells occurred in all pre - or postnatal stages. The findings indicated a biphasic apoptotic activity in the endocrine pancreas during the lifetime of rats. The first phase beg an at E19 and peaked at P5 accompanied by a considerable increase in Bak fl uorescence staining intensity, while the second phase began at P30 and peak ed at 18 months with increasing amounts of Fas and FasL staining intensitie s in the islet cells. The presented in situ data may be important for under standing the increased age-related vulnerability of islet cells and for stu dies of isolated and cultivated rat islets.