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Rubey, M. ; Chhabra, N.F. ; Gradinger, D. ; Sanz-Moreno, A. ; Lickert, H. ; Przemeck, G.K.H. ; Hrabě de Angelis, M.

DLL1- and DLL4-mediated Notch signaling is essential for adult pancreatic islet homeostasis.

Diabetes 69, 915-926 (2020)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Green
Genes of the Notch signaling pathway are expressed in different cell types and organs at different time points during embryonic development and adulthood. The Notch ligand Delta-like 1 (DLL1) controls the decision between endocrine and exocrine fates of multipotent progenitors in the developing pancreas, and loss of Dll1 leads to premature endocrine differentiation. However, the role of Delta-Notch signaling in adult tissue homeostasis is not well understood. Here, we describe the spatial expression pattern of Notch pathway components in adult murine pancreatic islets and show that DLL1 and DLL4 are specifically expressed in beta-cells, whereas JAGGED1 is expressed in alpha-cells. We show that mice lacking both DLL1 and DLL4 in adult beta-cells display improved glucose tolerance, increased glucose-stimulated insulin secretion, and hyperglucagonemia. In contrast, overexpression of the intracellular domain of DLL1 in adult murine pancreatic beta-cells results in impaired glucose tolerance and reduced insulin secretion, both in vitro and in vivo. These results suggest that Notch ligands play specific roles in the adult pancreas and highlight a novel function of the Delta/Notch pathway in beta-cell insulin secretion.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Beta-cell Identity; Delta-like 4; Ligand; Exchange; Domain; Proliferation; Delta-like-1; Inhibition; Activation; Insights
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 69, Issue: 5, Pages: 915-926 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Diabetes and Regeneration Research (IDR)