Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Davies, Emma L., Abdel-Wahab, Yasser H. A., Flatt, Peter R., Bailey, Clifford J.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2001
Materias:
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
_version_ 1782157583240396800
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
work_keys_str_mv AT daviesemmal functionalenhancementofelectrofusionderivedbrinbd11insulinsecretingcellsafterimplantationintodiabeticmice
AT abdelwahabyasserha functionalenhancementofelectrofusionderivedbrinbd11insulinsecretingcellsafterimplantationintodiabeticmice
AT flattpeterr functionalenhancementofelectrofusionderivedbrinbd11insulinsecretingcellsafterimplantationintodiabeticmice
AT baileycliffordj functionalenhancementofelectrofusionderivedbrinbd11insulinsecretingcellsafterimplantationintodiabeticmice