| Title: |
Desmoglein-2 is important for islet function and β-cell survival |
| Authors: |
Myo Min, KK; Rojas-Canales, D; Penko, D; DeNichilo, M; Cockshell, MP; Ffrench, CB; Thompson, EJ; Asplund, O; Drogemuller, CJ; Prasad, RB; Groop, L; Grey, ST; Thomas, HE; Loudovaris, T; Kay, TW; Mahoney, MG; Jessup, CF; Coates, PT; Bonder, CS |
| Publisher Information: |
SPRINGERNATURE |
| Publication Year: |
2022 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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 (Dsg2lo/lo), we observed a significant reduction in the number of pancreatic islets and islet size, and consequently, there was less total insulin content per islet cluster. Dsg2lo/lo mice also exhibited a reduction in blood vessel barrier integrity, an increased incidence of streptozotocin-induced diabetes, and islets isolated from Dsg2lo/lo mice were more susceptible to cytokine-induced β-cell apoptosis. Following transplantation into diabetic mice, islets isolated from Dsg2lo/lo mice were less effective than their wildtype counterparts at curing diabetes. In vitro assays using the Beta-TC-6 murine β-cell line suggest that DSG2 supports the actin cytoskeleton as well as the release of cytokines and chemokines. Taken together, our study suggests that DSG2 is an under-appreciated regulator of β-cell function in pancreatic islets and that a better understanding of this adhesion molecule may provide new opportunities ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://hdl.handle.net/11343/335244 |
| Availability: |
https://hdl.handle.net/11343/335244 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.B5C78B7D |
| Database: |
BASE |