Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.

Parenteral delivery of long-Acting glucagon-like peptide-1 (GLP-1) mimetics has received much attention as a therapeutic option for diabetes. However, cell therapy-based GLP-1 treatments may provide a more physiological regulation of blood glucose. The present study assessed the effects of chronic G...

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Main Authors: Vasu, Srividya, Moffett, R. C., McCluskey, J. T., Hamid, Muhajir, Irwin, N., Flatt, P. R.
Format: Article
Language:English
English
Published: Nature Publishing Group 2013
Online Access:http://psasir.upm.edu.my/id/eprint/28127/1/Beneficial%20effects%20of%20parenteral%20GLP.pdf
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author Vasu, Srividya
Moffett, R. C.
McCluskey, J. T.
Hamid, Muhajir
Irwin, N.
Flatt, P. R.
author_facet Vasu, Srividya
Moffett, R. C.
McCluskey, J. T.
Hamid, Muhajir
Irwin, N.
Flatt, P. R.
author_sort Vasu, Srividya
collection UPM
description Parenteral delivery of long-Acting glucagon-like peptide-1 (GLP-1) mimetics has received much attention as a therapeutic option for diabetes. However, cell therapy-based GLP-1 treatments may provide a more physiological regulation of blood glucose. The present study assessed the effects of chronic GLP-1 delivery by cell therapy, using the GLP-1-secreting GLUTag cell line, in normoglycemic and streptozotocin-induced diabetic mice. GLUTag cell aggregates were transplanted into the subscapular region of mice. Over 30 days, cellular transplantation gave rise to encapsulated and well-vascularized growths, which contained immunoreactive GLP-1. Cell implantation was well tolerated and had no appreciable metabolic effects in normal mice. However, transplantation significantly (P<0.001) countered excessive food and fluid intake in diabetic mice and maintained normal body weight. Circulating glucose (P<0.01) and glucagon (P<0.05) were significantly reduced and plasma insulin and GLP-1 dramatically increased. This was associated with significantly (P<0.01) improved glucose tolerance in diabetic mice. Histological examination of the pancreata of these mice revealed elevations (P<0.001) in islet and β-cell area, with reduced (P<0.001) -cell area. Increased β-cell mass reflected the enhanced proliferation relative to apoptosis. These studies emphasize the potential of chronic GLP-1 delivery by cell therapy as a potential therapeutic option for diabetes.
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spelling upm.eprints-281272015-10-07T03:54:11Z http://psasir.upm.edu.my/id/eprint/28127/ Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice. Vasu, Srividya Moffett, R. C. McCluskey, J. T. Hamid, Muhajir Irwin, N. Flatt, P. R. Parenteral delivery of long-Acting glucagon-like peptide-1 (GLP-1) mimetics has received much attention as a therapeutic option for diabetes. However, cell therapy-based GLP-1 treatments may provide a more physiological regulation of blood glucose. The present study assessed the effects of chronic GLP-1 delivery by cell therapy, using the GLP-1-secreting GLUTag cell line, in normoglycemic and streptozotocin-induced diabetic mice. GLUTag cell aggregates were transplanted into the subscapular region of mice. Over 30 days, cellular transplantation gave rise to encapsulated and well-vascularized growths, which contained immunoreactive GLP-1. Cell implantation was well tolerated and had no appreciable metabolic effects in normal mice. However, transplantation significantly (P<0.001) countered excessive food and fluid intake in diabetic mice and maintained normal body weight. Circulating glucose (P<0.01) and glucagon (P<0.05) were significantly reduced and plasma insulin and GLP-1 dramatically increased. This was associated with significantly (P<0.01) improved glucose tolerance in diabetic mice. Histological examination of the pancreata of these mice revealed elevations (P<0.001) in islet and β-cell area, with reduced (P<0.001) -cell area. Increased β-cell mass reflected the enhanced proliferation relative to apoptosis. These studies emphasize the potential of chronic GLP-1 delivery by cell therapy as a potential therapeutic option for diabetes. Nature Publishing Group 2013 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/28127/1/Beneficial%20effects%20of%20parenteral%20GLP.pdf Vasu, Srividya and Moffett, R. C. and McCluskey, J. T. and Hamid, Muhajir and Irwin, N. and Flatt, P. R. (2013) Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice. Gene Therapy, 20 (11). pp. 1077-1084. ISSN 0969-7128; ESSN: 1476-5462 http://www.nature.com/gt/journal/v20/n11/index.html 10.1038/gt.2013.33 English
spellingShingle Vasu, Srividya
Moffett, R. C.
McCluskey, J. T.
Hamid, Muhajir
Irwin, N.
Flatt, P. R.
Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.
title Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.
title_full Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.
title_fullStr Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.
title_full_unstemmed Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.
title_short Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.
title_sort beneficial effects of parenteral glp 1 delivery by cell therapy in insulin deficient streptozotocin diabetic mice
url http://psasir.upm.edu.my/id/eprint/28127/1/Beneficial%20effects%20of%20parenteral%20GLP.pdf
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