A Preconditioning Regimen With a PKC epsilon Activator Improves Islet Graft Function in a Mouse Transplant Model CELL TRANSPLANTATION Hamilton, D., Rugg, C., Davis, N., Kvezereli, M., Tafti, B. A., Busque, S., Fontaine, M. 2014; 23 (7): 913-919


BACKGROUND: Transplantation of islets isolated from deceased donor pancreata is an attractivemethod of ß cell replacement therapy for patients with type 1 diabetes (T1D). However the loss of islet cell viability and function during the peritransplant period is a limiting factor to long-term islet engraftment. Activation of the isoenzyme PKCe may improve islet survival and function. The currentstudy assesses the effects of PKC eactivation on islet graft function in a syngeneic streptozotocininduced diabetic mouse model.METHODS: Islets were isolated from wild-type BALB/c mice preconditioned with either a PKCeactivator (?eRACK) or a TAT carrier control peptide. Islets were further treated with the same agents during isolation, purification, and incubation prior to transplantation. 275 islet equivalents were transplanted under the kidney capsule of streptozotocin-induced diabetic BALB/c mice. Islet function was assessed by measurement of blood glucose levels every 3 days for 42 days after transplant and through an intra peritoneal glucose tolerance test (IPGTT).RESULTS: The time for return to euglycemia in mice transplanted with islets treated with ?eRACK was improved at 14 +/- 6 days versus 21+/- 6 days with TAT-treated islets. The IPGTT showed a 50% reduction in the area under the curve associated with an improved insulin response in mice transplanted with ?eRACK-treated islets compared to TAT-treated islets.CONCLUSION: A preconditioning regimen using PKCe agonist before pancreatic recovery and during islet isolation improves islet graft function and resistance to high glucose stress after transplantation.

View details for DOI 10.3727/096368913X665567

View details for Web of Science ID 000337989700010

View details for PubMedID 23562311