E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets

<b>Background:</b> Pig islets have the potential to address the limited supply of human islets available for transplantation. However, the knowledge of the biology of pig islets is currently limited. Thus, this study evaluated the molecules involved in cell-to-cell adhesion and insulin s...

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Main Authors: Kieran Purich, Josue Rodriguez Silva, Wenlong Huang, James Wickware, Thomas Williams, Adnan Black, Jeongbeen Kim, David Fernandez Chapa, Sudha Bhavanam, David Bigam, Daniel Schiller, Gina R. Rayat
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/3/627
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author Kieran Purich
Josue Rodriguez Silva
Wenlong Huang
James Wickware
Thomas Williams
Adnan Black
Jeongbeen Kim
David Fernandez Chapa
Sudha Bhavanam
David Bigam
Daniel Schiller
Gina R. Rayat
author_facet Kieran Purich
Josue Rodriguez Silva
Wenlong Huang
James Wickware
Thomas Williams
Adnan Black
Jeongbeen Kim
David Fernandez Chapa
Sudha Bhavanam
David Bigam
Daniel Schiller
Gina R. Rayat
author_sort Kieran Purich
collection DOAJ
description <b>Background:</b> Pig islets have the potential to address the limited supply of human islets available for transplantation. However, the knowledge of the biology of pig islets is currently limited. Thus, this study evaluated the molecules involved in cell-to-cell adhesion and insulin secretion pathways during the in vitro development of neonatal pig islets to understand the tissue we hope to use as a possible solution to the shortage of human islets for transplantation. <b>Methods</b>: Through RT-qPCR, immunoassays, and assessments of islet function, we explored the expression of E-cadherin and its correlation with the molecules involved in the insulin secretion pathway including GTPase, RAC1, and the membrane fusion protein SNAP25 during neonatal pig islet development. <b>Results</b>: Despite no significant difference observed in gross morphology and viability, as well as variable expression of RAC1, insulin, and SNAP25 in islets from 1-, 3-, and 7-day-old neonatal pigs, there was an apparent trend towards improved function in islets obtained from 3- and 7-day-old pigs compared with 1-day-old pigs. In the presence of 30 mM KCl, the amount of insulin secreted by islets from 3- and 7-day-old pigs but not from 1-day-old pigs was increased. Disruption of E-cadherin interactions with monoclonal antibodies resulted in decreased insulin secretion capacity of islets from 3-day old pigs. <b>Conclusions</b>: Our results show that blocking E-cadherin interactions with monoclonal antibodies resulted in disrupted peri-islet capsule and impaired islet insulin secretion under high glucose conditions. Thus, E-cadherin is important in the in vitro postnatal development and function of pig islets.
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spelling doaj-art-d4e7613abe81496caec4c0a8bfa882522025-08-20T02:42:35ZengMDPI AGBiomedicines2227-90592025-03-0113362710.3390/biomedicines13030627E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig IsletsKieran Purich0Josue Rodriguez Silva1Wenlong Huang2James Wickware3Thomas Williams4Adnan Black5Jeongbeen Kim6David Fernandez Chapa7Sudha Bhavanam8David Bigam9Daniel Schiller10Gina R. Rayat11Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2B7, Canada<b>Background:</b> Pig islets have the potential to address the limited supply of human islets available for transplantation. However, the knowledge of the biology of pig islets is currently limited. Thus, this study evaluated the molecules involved in cell-to-cell adhesion and insulin secretion pathways during the in vitro development of neonatal pig islets to understand the tissue we hope to use as a possible solution to the shortage of human islets for transplantation. <b>Methods</b>: Through RT-qPCR, immunoassays, and assessments of islet function, we explored the expression of E-cadherin and its correlation with the molecules involved in the insulin secretion pathway including GTPase, RAC1, and the membrane fusion protein SNAP25 during neonatal pig islet development. <b>Results</b>: Despite no significant difference observed in gross morphology and viability, as well as variable expression of RAC1, insulin, and SNAP25 in islets from 1-, 3-, and 7-day-old neonatal pigs, there was an apparent trend towards improved function in islets obtained from 3- and 7-day-old pigs compared with 1-day-old pigs. In the presence of 30 mM KCl, the amount of insulin secreted by islets from 3- and 7-day-old pigs but not from 1-day-old pigs was increased. Disruption of E-cadherin interactions with monoclonal antibodies resulted in decreased insulin secretion capacity of islets from 3-day old pigs. <b>Conclusions</b>: Our results show that blocking E-cadherin interactions with monoclonal antibodies resulted in disrupted peri-islet capsule and impaired islet insulin secretion under high glucose conditions. Thus, E-cadherin is important in the in vitro postnatal development and function of pig islets.https://www.mdpi.com/2227-9059/13/3/627adult pig isletsneonatal pig isletsE-cadheringlucose-stimulated insulin secretionin vitro culture
spellingShingle Kieran Purich
Josue Rodriguez Silva
Wenlong Huang
James Wickware
Thomas Williams
Adnan Black
Jeongbeen Kim
David Fernandez Chapa
Sudha Bhavanam
David Bigam
Daniel Schiller
Gina R. Rayat
E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets
Biomedicines
adult pig islets
neonatal pig islets
E-cadherin
glucose-stimulated insulin secretion
in vitro culture
title E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets
title_full E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets
title_fullStr E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets
title_full_unstemmed E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets
title_short E-Cadherin Is Important in the In Vitro Postnatal Development and Function of Pig Islets
title_sort e cadherin is important in the in vitro postnatal development and function of pig islets
topic adult pig islets
neonatal pig islets
E-cadherin
glucose-stimulated insulin secretion
in vitro culture
url https://www.mdpi.com/2227-9059/13/3/627
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