Desmoglein-2 is Important for Islet Function and β-Cell Survival

Authors

Kay K. Myo Min, University of South Australia and SA Pathology
Darling Rojas-Canales, Flinders Medical Centre
Daniella Penko, University of Adelaide
Mark DeNichilo, University of South Australia and SA Pathology
Michaelia P. Cockshell, University of South Australia and SA Pathology
Charlie B. Ffrench, University of South Australia and SA Pathology
Emma J. Thompson, University of South Australia and SA Pathology
Olof Asplund, Lund University
Christopher J. Drogemuller, University of Adelaide
Rashmi B. Prasad, Lund University
Leif Groop, Lund University
Shane T Grey, Garvan Institute of Medical Research
Helen E. Thomas, St Vincent’s Institute of Medical Research & the University of Melbourne
Thomas Loudovaris, St Vincent’s Institute of Medical Research & the University of Melbourne
Thomas W. Kay, St Vincent’s Institute of Medical Research & the University of Melbourne
My G. Mahoney, Thomas Jefferson UniversityFollow
Claire F. Jessup, Flinders Medical Centre
P. Toby Coates, University of Adelaide
Claudine S. Bonder, University of South Australia and SA Pathology

Document Type

Article

Publication Date

10-29-2022

Comments

This is the author's final published version in Cell Death and Disease, Volume 13, Issue 10, October 2022, Article number 911.

The published version is available at https://doi.org/10.1038/s41419-022-05326-2. Copyright © The Author(s) 2022.

Abstract

Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lacking Dsg2 were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes in a syngeneic transplantation model. Herein, we have identified DSG2 as a previously unrecognized adhesion molecule that supports β-cells. Furthermore, we reveal that DSG2 is within the top 10 percent of all genes expressed by human pancreatic islets and is expressed by the insulin-producing β-cells but not the somatostatin-producing δ-cells. In a Dsg2 loss-of-function mice (Dsg2

Recommended Citation

Myo Min, Kay K.; Rojas-Canales, Darling; Penko, Daniella; DeNichilo, Mark; Cockshell, Michaelia P.; Ffrench, Charlie B.; Thompson, Emma J.; Asplund, Olof; Drogemuller, Christopher J.; Prasad, Rashmi B.; Groop, Leif; Grey, Shane T; Thomas, Helen E.; Loudovaris, Thomas; Kay, Thomas W.; Mahoney, My G.; Jessup, Claire F.; Coates, P. Toby; and Bonder, Claudine S., "Desmoglein-2 is Important for Islet Function and β-Cell Survival" (2022). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 170.
https://jdc.jefferson.edu/dcbfp/170

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

36309486

Language

English