Human, nonhuman primate, and rat pancreatic islets express erythropoietin receptors1

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Abstract
Erythropoietin (EPO) promotes survival in a variety of cells by mediating antiapoptotic signals through the EPO receptor (R). The authors examined pancreatic islets for the presence of EPO-R to determine whether these cells are protected by EPO from cytokine-induced apoptosis. Reverse-transcriptase polymerase chain reaction, immunohistology, and Western blots were used to establish the presence and localization of EPO-R on rat, nonhuman primate, and human islets. Islets were exposed to cytokines in the presence and absence of recombinant EPO and apoptosis was measured using a terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay followed by fluorescence-activated cell sorter analysis. Glucose stimulation indices were measured to assess the effect of EPO on islet function. The presence of EPO-R was demonstrated on islets regardless of species. Recombinant EPO protected islets in culture from cytokine-induced apoptosis in a dose-dependent manner. Furthermore, the presence of EPO in the media does not adversely affect islet function. This is the first demonstration that pancreatic islets express EPO-R and that EPO may prevent islet-cell apoptosis in culture. In vivo trials to evaluate the potential of long-term expression of EPO to augment islet survival in transplantation are underway.