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Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice
Electrofusion-derived BRIN-BD11 cells are glucosesensitive insulin-secreting cells which provide an archetypal bioengineered surrogate β-cell for insulin replacement therapy in diabetes mellitus, 5x10(6) BRIN-BD11 cells were implanted intraperitoneally into severely hyperglycaemic (>24mmol/l) str...
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2001
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478526/ https://www.ncbi.nlm.nih.gov/pubmed/12369723 http://dx.doi.org/10.1155/EDR.2001.29 |
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author | Davies, Emma L. Abdel-Wahab, Yasser H. A. Flatt, Peter R. Bailey, Clifford J. |
author_facet | Davies, Emma L. Abdel-Wahab, Yasser H. A. Flatt, Peter R. Bailey, Clifford J. |
author_sort | Davies, Emma L. |
collection | PubMed |
description | Electrofusion-derived BRIN-BD11 cells are glucosesensitive insulin-secreting cells which provide an archetypal bioengineered surrogate β-cell for insulin replacement therapy in diabetes mellitus, 5x10(6) BRIN-BD11 cells were implanted intraperitoneally into severely hyperglycaemic (>24mmol/l) streptozotocin-induced insulin-treated diabetic athymic nude (nu/nu) mice. The implants reduced hyperglycaemia such that insulin injections were discontinued by 5–16 days (<17mmol/l) and normoglycaemia (<9mmol/l) was achieved by 7–20 days. Implanted cells were removed after 28 days and re-established in culture. After re-culture for 20 days, glucose-stimulated (16.7mmol/l) insulin release was enhanced by 121% (p<0.001) compared to non-implanted cells. Insulin responses to glucagon-like peptide-1 (10(−9)mol/l), cholecystokinin-8 (10(−8) mol/l) and L-alanine (10 mmol/l) were increased by 32%, 31% and 68% respectively (p<0.05–0.01). Insulin content of the cells was 148% greater at 20 days after re-culture than before implantation (p<0.001), but basal insulin release (at 5.6 mmol/l glucose) was not changed. After re-culture for 40 days, insulin content declined to 68% of the content before implantation (p<0.01), although basal insulin release was unchanged. However, the insulin secretory responses to glucose, glucagonlike peptide-1, cholecystokinin-8 and L-alanine were decreased after 40 days of re-culture to 65%, 72%, 73% and 42% respectively of the values before implantation (p<0.05–0.01). The functional enhancement of electrofusion-derived surrogate β-cells that were re-cultured for 20 days after implantation and restoration of normoglycaemia indicates that the in vivo environment could greatly assist β-cell engineering approaches to therapy for diabetes. |
format | Text |
id | pubmed-2478526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-24785262008-08-18 Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice Davies, Emma L. Abdel-Wahab, Yasser H. A. Flatt, Peter R. Bailey, Clifford J. Int J Exp Diabetes Res Research Article Electrofusion-derived BRIN-BD11 cells are glucosesensitive insulin-secreting cells which provide an archetypal bioengineered surrogate β-cell for insulin replacement therapy in diabetes mellitus, 5x10(6) BRIN-BD11 cells were implanted intraperitoneally into severely hyperglycaemic (>24mmol/l) streptozotocin-induced insulin-treated diabetic athymic nude (nu/nu) mice. The implants reduced hyperglycaemia such that insulin injections were discontinued by 5–16 days (<17mmol/l) and normoglycaemia (<9mmol/l) was achieved by 7–20 days. Implanted cells were removed after 28 days and re-established in culture. After re-culture for 20 days, glucose-stimulated (16.7mmol/l) insulin release was enhanced by 121% (p<0.001) compared to non-implanted cells. Insulin responses to glucagon-like peptide-1 (10(−9)mol/l), cholecystokinin-8 (10(−8) mol/l) and L-alanine (10 mmol/l) were increased by 32%, 31% and 68% respectively (p<0.05–0.01). Insulin content of the cells was 148% greater at 20 days after re-culture than before implantation (p<0.001), but basal insulin release (at 5.6 mmol/l glucose) was not changed. After re-culture for 40 days, insulin content declined to 68% of the content before implantation (p<0.01), although basal insulin release was unchanged. However, the insulin secretory responses to glucose, glucagonlike peptide-1, cholecystokinin-8 and L-alanine were decreased after 40 days of re-culture to 65%, 72%, 73% and 42% respectively of the values before implantation (p<0.05–0.01). The functional enhancement of electrofusion-derived surrogate β-cells that were re-cultured for 20 days after implantation and restoration of normoglycaemia indicates that the in vivo environment could greatly assist β-cell engineering approaches to therapy for diabetes. Hindawi Publishing Corporation 2001 /pmc/articles/PMC2478526/ /pubmed/12369723 http://dx.doi.org/10.1155/EDR.2001.29 Text en Copyright © 2001 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Davies, Emma L. Abdel-Wahab, Yasser H. A. Flatt, Peter R. Bailey, Clifford J. Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice |
title | Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice |
title_full | Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice |
title_fullStr | Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice |
title_full_unstemmed | Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice |
title_short | Functional Enhancement of Electrofusion-derived BRIN-BD11 Insulin-secreting Cells After Implantation into Diabetic Mice |
title_sort | functional enhancement of electrofusion-derived brin-bd11 insulin-secreting cells after implantation into diabetic mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478526/ https://www.ncbi.nlm.nih.gov/pubmed/12369723 http://dx.doi.org/10.1155/EDR.2001.29 |
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