Liraglutide, a long‐acting human glucagon‐like peptide 1 analogue, improves human islet survival in culture

Summary 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 thei...

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Veröffentlicht in:Transplant international 2010-03, Vol.23 (3), p.259-265
Hauptverfasser: Toso, Christian, McCall, Michael, Emamaullee, Juliet, Merani, Shaheed, Davis, Joy, Edgar, Ryan, Pawlick, Rena, Kin, Tatsuya, Knudsen, Lotte B., Shapiro, AM James
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container_end_page 265
container_issue 3
container_start_page 259
container_title Transplant international
container_volume 23
creator Toso, Christian
McCall, Michael
Emamaullee, Juliet
Merani, Shaheed
Davis, Joy
Edgar, Ryan
Pawlick, Rena
Kin, Tatsuya
Knudsen, Lotte B.
Shapiro, AM James
description Summary 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 μmol/l) was associated with a preservation of islet mass (significantly more islets at 24 and 48 h, compared to control; P ≤ 0.05 at 24 and 48 h) and with the presence of larger islets (P ≤ 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 μg/kg sc twice daily (P ≤ 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.
doi_str_mv 10.1111/j.1432-2277.2009.00984.x
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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 μmol/l) was associated with a preservation of islet mass (significantly more islets at 24 and 48 h, compared to control; P ≤ 0.05 at 24 and 48 h) and with the presence of larger islets (P ≤ 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 μg/kg sc twice daily (P ≤ 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. 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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 μmol/l) was associated with a preservation of islet mass (significantly more islets at 24 and 48 h, compared to control; P ≤ 0.05 at 24 and 48 h) and with the presence of larger islets (P ≤ 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 μg/kg sc twice daily (P ≤ 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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19821955</pmid><doi>10.1111/j.1432-2277.2009.00984.x</doi><tpages>7</tpages></addata></record>
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subjects Animals
Apoptosis - drug effects
culture
Female
function
glucagon
Glucagon-Like Peptide 1 - administration & dosage
Glucagon-Like Peptide 1 - analogs & derivatives
Glucagon-Like Peptide 1 - pharmacology
Graft Survival - drug effects
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - pharmacology
Insulin
Insulin - metabolism
islet
Islets of Langerhans - cytology
Islets of Langerhans - drug effects
Islets of Langerhans - metabolism
Islets of Langerhans Transplantation - methods
Liraglutide
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Pancreas
peptide
Tissue Culture Techniques
Transplantation, Heterologous
title Liraglutide, a long‐acting human glucagon‐like peptide 1 analogue, improves human islet survival in culture
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