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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2006-9-6
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pubmed:abstractText |
Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells. While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet alpha cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function. We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets. Here, we show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment. PC1/3 expression in alpha cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet beta cells. These results demonstrate a unique strategy for liberating GLP-1 from directly within the target organ and highlight the potential for up-regulating islet GLP-1 production as a means of treating diabetes.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-10440129,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-10580413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-10605628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-10749575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-10911004,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-11423477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-11703427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-11756324,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-12049785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-12145241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-12409292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-12540609,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-14960745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-15220193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-15677711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-15811484,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-8572216,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-8603757,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16938896-8947461
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13468-73
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16938896-Adenoviridae,
pubmed-meshheading:16938896-Animals,
pubmed-meshheading:16938896-Cell Culture Techniques,
pubmed-meshheading:16938896-Cell Line,
pubmed-meshheading:16938896-Cell Survival,
pubmed-meshheading:16938896-Diabetes Mellitus, Experimental,
pubmed-meshheading:16938896-Genetic Vectors,
pubmed-meshheading:16938896-Glucagon-Like Peptide 1,
pubmed-meshheading:16938896-Glucose,
pubmed-meshheading:16938896-Glucose Tolerance Test,
pubmed-meshheading:16938896-Insulin,
pubmed-meshheading:16938896-Interleukin-1,
pubmed-meshheading:16938896-Islets of Langerhans,
pubmed-meshheading:16938896-Islets of Langerhans Transplantation,
pubmed-meshheading:16938896-Mice,
pubmed-meshheading:16938896-Mice, Inbred C57BL,
pubmed-meshheading:16938896-Mice, Inbred Strains,
pubmed-meshheading:16938896-Proprotein Convertase 1,
pubmed-meshheading:16938896-Proprotein Convertase 2,
pubmed-meshheading:16938896-Transduction, Genetic
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pubmed:year |
2006
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pubmed:articleTitle |
Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1).
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pubmed:affiliation |
Laboratories of Molecular and Cellular Medicine, Departments of Cellular and Physiological Sciences and Surgery, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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