Dissociation between Fas expression and induction of apoptosis in human islets of Langerhans

Abstract

There is increasing evidence that inappropriate induction of apoptosis in pancreatic beta-cells may precede the development of type 1 diabetes in animal models and in man. One mechanism by which this has been proposed to occur involves up-regulation of the death receptor Fas on beta-cells, resulting in apoptosis of the Fas-bearing beta-cells upon ligation of the receptor. We have examined this hypothesis in isolated human islets of Langerhans and show that--in contrast to data obtained with rodent beta-cells--expression of Fas per se is not sufficient to allow induction of apoptosis upon addition of agonistic anti-Fas serum.

Effects of tyrosine kinase inhibitors on cell death induced by sodium fluoride and pertussis toxin in the pancreatic β‐cell line, RINm5F

“…The control of cell death in pancreatic β‐cells involves a number of interacting signalling pathways which converge to regulate the final effectors involved in the execution phase of apoptosis ( Loweth et al ., 1996 ; 1997 ; 1998 ; 2000 ; Harrison et al ., 1998 ; Mauricio & Mandrup‐Poulsen, 1998 ; Paraskevas et al ., 1998 ; Ishizuka et al ., 1999 ; Kay et al ., 2000 ). We have provided previous evidence that one such pathway involves a Ptx sensitive component (presumably a G‐protein) which acts to restrain the entry of the cells into apoptosis ( Loweth et al ., 1996 ).…”