Liraglutide, a long-acting human glucagon-like peptide 1 analogue, improves human islet survival in culture.
The culture of human islets is associated with approximately 10-20% islet loss, occasionally preventing transplantation. Preconditioning of the islets to improve postculture yields would be of immediate benefit, with the potential to increase both the number of transplanted patients and their metabolic reserve. In this study, the effect of liraglutide, a long-acting human glucagon-like peptide 1 analogue, on cultured human islets was examined. Culture with liraglutide (1 micromol/l) was associated with a preservation of islet mass (significantly more islets at 24 and 48 h, compared to control; P < or = 0.05 at 24 and 48 h) and with the presence of larger islets (P < or = 0.05 at 48 h). These observations were supported by reduced apoptosis rates after 24 h of treatment. We also demonstrated that human islet engraftment is improved in C57Bl/6-RAG(-/-) mice treated with liraglutide 200 microg/kg sc twice daily (P < or = 0.05), suggesting that liraglutide should be continued after transplantation. Overall, these data demonstrate the beneficial effect of liraglutide on cultured human islets, preserving islet mass. They support the design of clinical studies looking at the effect of liraglutide in clinical islet transplantation.
Toso
Christian
C
Clinical Islet Transplant Program, Department of Surgery, University of Alberta, Edmonton, AB, Canada. christian.toso@hcuge.ch
McCall
Michael
M
Emamaullee
Juliet
J
Merani
Shaheed
S
Davis
Joy
J
Edgar
Ryan
R
Pawlick
Rena
R
Kin
Tatsuya
T
Knudsen
Lotte B
LB
Shapiro
A M James
AM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D000069450:Liraglutide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D046509:Tissue Culture Techniques; D014183:Transplantation, Heterologous
D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1