Islet cell survival during isolation improved through protein kinase C epsilon activation.
Strategies inhibiting cell death signaling pathways may enhance the availability of islet transplantation for patients with type 1 diabetes mellitus. The epsilon isoform of protein kinase C (PKC epsilon) has been shown to have an anti-apoptotic effect in many cell types. The present study investigated whether activation of PKC epsilon may improve the yield of functional islet cells for transplantation. Islet cells were isolated from wild-type BALB/c mice preconditioned with either a PKC epsilon activator (psi epsilon RACK) or a TAT carrier control peptide and further treated with the same agents during isolation and in vitro for either 0, 1, 16, or 40 hours. Islet cells were assessed at each time point for viability, apoptosis, and function. psi epsilon RACK-treated islets showed significantly decreased islet cell death up to 40 hours after isolation compared with TAT-treated control islets. Beta-cell function in response to high glucose challenge remained unchanged.
Kvezereli
M
M
Department of Pathology, Stanford University, Stanford, California, USA.
Vallentin
A
A
Mochly-Rosen
D
D
Busque
S
S
Fontaine
M J
MJ
D000818:Animals; D018929:Cell Culture Techniques; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D004789:Enzyme Activation; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000201:enzymology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D020858:Tissue and Organ Harvesting / Q000379:methods
D051744:Protein Kinase C-epsilon