Human, nonhuman primate, and rat pancreatic islets express erythropoietin receptors.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fenjves
Elizabeth S
ES
Diabetes Research Institute, University Of Miami, School of Medicine, Miami, FL 33136, USA. efenjves@miami.edu.
Ochoa
M Sofia
MS
Cabrera
Over
O
Mendez
Armando J
AJ
Kenyon
Norma S
NS
Inverardi
Luca
L
Ricordi
Camillo
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011323:Primates; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007328:Insulin; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin