Effects of pancreas cold ischemia on islet function and quality.
We used a rat model of pancreas cold preservation to assess its effects on islets. Glands were surgically retrieved and stored in University of Wisconsin (UW) solution for 3 hours (Short) or 18 hours (Long) cold ischemia time (CIT). Islet yield was significantly lower in the Long-CIT than the Short-CIT group, as well as islet recovery after overnight culture (P < .01). Islet cell viability after isolation was significantly reduced in the Long-CIT group (P < .05). Reversal of diabetes following transplantation of suboptimal islet grafts occurred earlier in the Short-CIT group than the Long-CIT. All animals in the Short-CIT group and 80% in the Long-CIT group achieved euglycemia. Freshly isolated islets showed a significant increase of JNK and p38 (P < .05) phosphorylation in Long-CIT compared with Short-CIT. Histopathological assessment of the pancreas showed a significantly higher injury score. Proteomic analysis of pancreatic tissue led to identification of 5 proteins consistently differentially expressed between Short-CIT and Long-CIT. Better understanding of the molecular pathways involved in this phenomenon will be of assistance in defining targeted interventions to improve organ use in the clinical arena.
Pileggi
A
A
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. apileggi@med.miami.edu
Ribeiro
M M
MM
Hogan
A R
AR
Molano
R D
RD
Embury
J E
JE
Ichii
H
H
Cobianchi
L
L
Fornoni
A
A
Ricordi
C
C
Pastori
R L
RL
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002470:Cell Survival; D005978:Glutathione; D007328:Insulin; D007511:Ischemia; D007515:Islets of Langerhans / Q000166:cytology* / Q000473:pathology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019188:Organ Preservation Solutions; D010179:Pancreas / Q000098:blood supply / Q000166:cytology* / Q000473:pathology; D010770:Phosphotransferases / Q000378:metabolism; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D020858:Tissue and Organ Harvesting / Q000379:methods
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D010770:Phosphotransferases; D020929:Mitogen-Activated Protein Kinase Kinases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose