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 |
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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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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.</description><identifier>ISSN: 0934-0874</identifier><identifier>EISSN: 1432-2277</identifier><identifier>DOI: 10.1111/j.1432-2277.2009.00984.x</identifier><identifier>PMID: 19821955</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>Transplant international, 2010-03, Vol.23 (3), p.259-265</ispartof><rights>2009 The Authors. Journal compilation © 2009 European Society for Organ Transplantation</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3954-6625600777c91b5bbe81c40a753ccda8fe04cda9c9e62ebed648c9f20a876d963</citedby><cites>FETCH-LOGICAL-c3954-6625600777c91b5bbe81c40a753ccda8fe04cda9c9e62ebed648c9f20a876d963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1432-2277.2009.00984.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1432-2277.2009.00984.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19821955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toso, Christian</creatorcontrib><creatorcontrib>McCall, Michael</creatorcontrib><creatorcontrib>Emamaullee, Juliet</creatorcontrib><creatorcontrib>Merani, Shaheed</creatorcontrib><creatorcontrib>Davis, Joy</creatorcontrib><creatorcontrib>Edgar, Ryan</creatorcontrib><creatorcontrib>Pawlick, Rena</creatorcontrib><creatorcontrib>Kin, Tatsuya</creatorcontrib><creatorcontrib>Knudsen, Lotte B.</creatorcontrib><creatorcontrib>Shapiro, AM James</creatorcontrib><title>Liraglutide, a long‐acting human glucagon‐like peptide 1 analogue, improves human islet survival in culture</title><title>Transplant international</title><addtitle>Transpl Int</addtitle><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.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>culture</subject><subject>Female</subject><subject>function</subject><subject>glucagon</subject><subject>Glucagon-Like Peptide 1 - administration & dosage</subject><subject>Glucagon-Like Peptide 1 - analogs & derivatives</subject><subject>Glucagon-Like Peptide 1 - pharmacology</subject><subject>Graft Survival - drug effects</subject><subject>Humans</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>islet</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>Islets of Langerhans Transplantation - methods</subject><subject>Liraglutide</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Middle Aged</subject><subject>Pancreas</subject><subject>peptide</subject><subject>Tissue Culture Techniques</subject><subject>Transplantation, Heterologous</subject><issn>0934-0874</issn><issn>1432-2277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkduKFDEQhoMo7rj6ChLwwhu7zaE7B_BGFg8LA4Ks1yGdrmkzprvHpDPu3vkIPqNPYtoZFLwyEKpIfX8lqR8hTElNy3q5r2nDWcWYlDUjRNdlq6a-vYc2fwr30YZo3lREyeYCPUppTwhhqiUP0QXVilHdths0b320Q8iL7-EFtjjM0_Dz-w_rFj8N-HMe7YRL2dlhnsp58F8AH-Cw4phiO9kwD7ko_XiI8xHSWeJTgAWnHI_-aAP2E3Y5LDnCY_RgZ0OCJ-d4iT69fXNz9b7afnh3ffV6Wzmu26YSgrWCECml07Rruw4UdQ2xsuXO9VbtgDQlaqdBMOigF41yeseIVVL0WvBL9PzUtzzra4a0mNEnByHYCeacjOScU00lKeSzf8j9nGP5WDJUCqG0KFMrlDpRLs4pRdiZQ_SjjXeGErN6YvZmHb1ZR29WT8xvT8xtkT49X5C7Efq_wrMJBXh1Ar75AHf_3djcfLwuCf8FNZ2dCQ</recordid><startdate>201003</startdate><enddate>201003</enddate><creator>Toso, Christian</creator><creator>McCall, Michael</creator><creator>Emamaullee, Juliet</creator><creator>Merani, Shaheed</creator><creator>Davis, Joy</creator><creator>Edgar, Ryan</creator><creator>Pawlick, Rena</creator><creator>Kin, Tatsuya</creator><creator>Knudsen, Lotte B.</creator><creator>Shapiro, AM James</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201003</creationdate><title>Liraglutide, a long‐acting human glucagon‐like peptide 1 analogue, improves human islet survival in culture</title><author>Toso, Christian ; McCall, Michael ; Emamaullee, Juliet ; Merani, Shaheed ; Davis, Joy ; Edgar, Ryan ; Pawlick, Rena ; Kin, Tatsuya ; Knudsen, Lotte B. ; Shapiro, AM James</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3954-6625600777c91b5bbe81c40a753ccda8fe04cda9c9e62ebed648c9f20a876d963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>culture</topic><topic>Female</topic><topic>function</topic><topic>glucagon</topic><topic>Glucagon-Like Peptide 1 - administration & dosage</topic><topic>Glucagon-Like Peptide 1 - analogs & derivatives</topic><topic>Glucagon-Like Peptide 1 - pharmacology</topic><topic>Graft Survival - drug effects</topic><topic>Humans</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>islet</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>Islets of Langerhans Transplantation - methods</topic><topic>Liraglutide</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Middle Aged</topic><topic>Pancreas</topic><topic>peptide</topic><topic>Tissue Culture Techniques</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toso, Christian</creatorcontrib><creatorcontrib>McCall, Michael</creatorcontrib><creatorcontrib>Emamaullee, Juliet</creatorcontrib><creatorcontrib>Merani, Shaheed</creatorcontrib><creatorcontrib>Davis, Joy</creatorcontrib><creatorcontrib>Edgar, Ryan</creatorcontrib><creatorcontrib>Pawlick, Rena</creatorcontrib><creatorcontrib>Kin, Tatsuya</creatorcontrib><creatorcontrib>Knudsen, Lotte B.</creatorcontrib><creatorcontrib>Shapiro, AM James</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplant international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toso, Christian</au><au>McCall, Michael</au><au>Emamaullee, Juliet</au><au>Merani, Shaheed</au><au>Davis, Joy</au><au>Edgar, Ryan</au><au>Pawlick, Rena</au><au>Kin, Tatsuya</au><au>Knudsen, Lotte B.</au><au>Shapiro, AM James</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liraglutide, a long‐acting human glucagon‐like peptide 1 analogue, improves human islet survival in culture</atitle><jtitle>Transplant international</jtitle><addtitle>Transpl Int</addtitle><date>2010-03</date><risdate>2010</risdate><volume>23</volume><issue>3</issue><spage>259</spage><epage>265</epage><pages>259-265</pages><issn>0934-0874</issn><eissn>1432-2277</eissn><abstract>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.</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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