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Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide

Type 1 diabetes results from the loss of pancreatic β cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost β cells with stem cell-derived β cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostas...

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Autores principales: Amin, Md Lutful, Deng, Kylie, Tran, Hien A., Singh, Reena, Rnjak-Kovacina, Jelena, Thorn, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774350/
https://www.ncbi.nlm.nih.gov/pubmed/36550929
http://dx.doi.org/10.3390/bioengineering9120722
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author Amin, Md Lutful
Deng, Kylie
Tran, Hien A.
Singh, Reena
Rnjak-Kovacina, Jelena
Thorn, Peter
author_facet Amin, Md Lutful
Deng, Kylie
Tran, Hien A.
Singh, Reena
Rnjak-Kovacina, Jelena
Thorn, Peter
author_sort Amin, Md Lutful
collection PubMed
description Type 1 diabetes results from the loss of pancreatic β cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost β cells with stem cell-derived β cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostasis. However, to achieve this goal of restoration of glucose balance requires work to optimise β cell function within implants. We know that native β cell function is enhanced by cell–cell and cell–extracellular matrix interactions within the islets of Langerhans. Reproducing these interactions in 2D, such as culture on matrix proteins, does enhance insulin secretion. However, the impact of matrix proteins on the 3D organoids that would be in implants has not been widely studied. Here, we use native β cells that are dispersed from islets and reaggregated into small spheroids. We show these β cell spheroids have enhanced glucose-dependent insulin secretion when embedded into softer alginate hydrogels conjugated with RGD peptide (a common motif in extracellular matrix proteins). Embedding into alginate–RGD causes activation of integrin responses and repositioning of liprin, a protein that controls insulin secretion. We conclude that insulin secretion from β cell spheroids can be enhanced through manipulation of the surrounding environment.
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spelling pubmed-97743502022-12-23 Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide Amin, Md Lutful Deng, Kylie Tran, Hien A. Singh, Reena Rnjak-Kovacina, Jelena Thorn, Peter Bioengineering (Basel) Article Type 1 diabetes results from the loss of pancreatic β cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost β cells with stem cell-derived β cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostasis. However, to achieve this goal of restoration of glucose balance requires work to optimise β cell function within implants. We know that native β cell function is enhanced by cell–cell and cell–extracellular matrix interactions within the islets of Langerhans. Reproducing these interactions in 2D, such as culture on matrix proteins, does enhance insulin secretion. However, the impact of matrix proteins on the 3D organoids that would be in implants has not been widely studied. Here, we use native β cells that are dispersed from islets and reaggregated into small spheroids. We show these β cell spheroids have enhanced glucose-dependent insulin secretion when embedded into softer alginate hydrogels conjugated with RGD peptide (a common motif in extracellular matrix proteins). Embedding into alginate–RGD causes activation of integrin responses and repositioning of liprin, a protein that controls insulin secretion. We conclude that insulin secretion from β cell spheroids can be enhanced through manipulation of the surrounding environment. MDPI 2022-11-23 /pmc/articles/PMC9774350/ /pubmed/36550929 http://dx.doi.org/10.3390/bioengineering9120722 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Amin, Md Lutful
Deng, Kylie
Tran, Hien A.
Singh, Reena
Rnjak-Kovacina, Jelena
Thorn, Peter
Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide
title Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide
title_full Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide
title_fullStr Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide
title_full_unstemmed Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide
title_short Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide
title_sort glucose-dependent insulin secretion from β cell spheroids is enhanced by embedding into softer alginate hydrogels functionalised with rgd peptide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774350/
https://www.ncbi.nlm.nih.gov/pubmed/36550929
http://dx.doi.org/10.3390/bioengineering9120722
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