Effect of JNK inhibitor during islet isolation and transplantation.
Although islet transplantation has been remarkably improved by the Edmonton protocol, the insulin independence rate after islet transplantation from one donor pancreas has remained low. The c-Jun NH2-terminal kinases (JNKs) are classic stress-activated protein kinases; many cellular stresses have been shown to stimulate JNK activation. JNK in the pancreas is activated during brain death, pancreas procurement, and organ preservation, and its activity is progressively increased during the isolation procedure. Moreover, JNK activity in the transplanted liver after islet transplantation increases markedly within 24 hours. In this study, we show the effect of a JNK inhibitor during islet isolation and transplantation. Use of the JNK inhibitor in pancreas preservation, islet culture, and/or islet transplantation prevents islet cell apoptosis and improves islet graft function. These findings suggest that inhibition of JNK could prevent the impairment of islet cells and improve outcomes after pancreatic islet transplantation.
Noguchi
H
H
Baylor Institute for Immunology Research/Baylor All Saints Medical Center, Baylor Research Institute, Fort Worth, Texas 75204, USA. hirofumn@baylorhealth.edu
Matsumoto
S
S
Kobayashi
N
N
Hayashi
S
S
Iwanaga
Y
Y
Nagata
H
H
Jackson
A
A
Naziruddin
B
B
Okitsu
T
T
Levy
M F
MF
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D051379:Mice; D016896:Treatment Outcome
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D048670:MAP Kinase Kinase 4