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
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.
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