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Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets

BACKGROUND: In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the imm...

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Autores principales: Buchwald, Peter, Cechin, Sirlene R, Weaver, Jessica D, Stabler, Cherie L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403786/
https://www.ncbi.nlm.nih.gov/pubmed/25889474
http://dx.doi.org/10.1186/s12938-015-0021-9
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author Buchwald, Peter
Cechin, Sirlene R
Weaver, Jessica D
Stabler, Cherie L
author_facet Buchwald, Peter
Cechin, Sirlene R
Weaver, Jessica D
Stabler, Cherie L
author_sort Buchwald, Peter
collection PubMed
description BACKGROUND: In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. Islet encapsulation using various techniques and materials has been and is being extensively explored as a possible approach. Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets. METHODS: To improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets in general and of micro-encapsulated islets in particular, we performed dynamic perifusion experiments with frequent sampling. We used unencapsulated and microencapsulated murine islets in parallel and fitted the results with a complex local concentration-based finite element method (FEM) computational model. RESULTS: The high-resolution dynamic perifusion experiments allowed good characterization of the first-phase and second-phase insulin secretion, and we observed a slightly delayed and blunted first-phase insulin response for microencapsulated islets when compared to free islets. Insulin secretion profiles of both free and encapsulated islets could be fitted well by a COMSOL Multiphysics model that couples hormone secretion and nutrient consumption kinetics with diffusive and convective transport. This model, which was further validated and calibrated here, can be used for arbitrary geometries and glucose stimulation sequences and is well suited for the quantitative characterization of the insulin response of cultured, perifused, transplanted, or encapsulated islets. CONCLUSIONS: The present high-resolution GSIR experiments allowed for direct characterization of the effect microencapsulation has on the time-profile of insulin secretion. The multiphysics model, further validated here with the help of these experimental results, can be used to increase our understanding of the challenges that have to be faced in the design of bioartificial pancreas-type devices and to advance their further optimization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12938-015-0021-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-44037862015-04-21 Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets Buchwald, Peter Cechin, Sirlene R Weaver, Jessica D Stabler, Cherie L Biomed Eng Online Research BACKGROUND: In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. Islet encapsulation using various techniques and materials has been and is being extensively explored as a possible approach. Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets. METHODS: To improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets in general and of micro-encapsulated islets in particular, we performed dynamic perifusion experiments with frequent sampling. We used unencapsulated and microencapsulated murine islets in parallel and fitted the results with a complex local concentration-based finite element method (FEM) computational model. RESULTS: The high-resolution dynamic perifusion experiments allowed good characterization of the first-phase and second-phase insulin secretion, and we observed a slightly delayed and blunted first-phase insulin response for microencapsulated islets when compared to free islets. Insulin secretion profiles of both free and encapsulated islets could be fitted well by a COMSOL Multiphysics model that couples hormone secretion and nutrient consumption kinetics with diffusive and convective transport. This model, which was further validated and calibrated here, can be used for arbitrary geometries and glucose stimulation sequences and is well suited for the quantitative characterization of the insulin response of cultured, perifused, transplanted, or encapsulated islets. CONCLUSIONS: The present high-resolution GSIR experiments allowed for direct characterization of the effect microencapsulation has on the time-profile of insulin secretion. The multiphysics model, further validated here with the help of these experimental results, can be used to increase our understanding of the challenges that have to be faced in the design of bioartificial pancreas-type devices and to advance their further optimization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12938-015-0021-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-28 /pmc/articles/PMC4403786/ /pubmed/25889474 http://dx.doi.org/10.1186/s12938-015-0021-9 Text en © Buchwald et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Buchwald, Peter
Cechin, Sirlene R
Weaver, Jessica D
Stabler, Cherie L
Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
title Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
title_full Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
title_fullStr Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
title_full_unstemmed Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
title_short Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
title_sort experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403786/
https://www.ncbi.nlm.nih.gov/pubmed/25889474
http://dx.doi.org/10.1186/s12938-015-0021-9
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