DLL1- and DLL4-Mediated Notch Signaling Is Essential for Adult Pancreatic Islet Homeostasis
-
- Marina Rubey
- Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
-
- Nirav Florian Chhabra
- Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
-
- Daniel Gradinger
- Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
-
- Adrián Sanz-Moreno
- Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
-
- Heiko Lickert
- German Center for Diabetes Research, Neuherberg, Germany
-
- Gerhard K.H. Przemeck
- Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
-
- Martin Hrabě de Angelis
- Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
抄録
<jats:p>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 β-cells, whereas JAGGED1 is expressed in α-cells. We show that mice lacking both DLL1 and DLL4 in adult β-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 β-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 β-cell insulin secretion.</jats:p>
収録刊行物
-
- Diabetes
-
Diabetes 69 (5), 915-926, 2020-02-06
American Diabetes Association
