PgmNr M5097: Dll1- and Dll4-mediated Notch signaling in adult pancreatic β-cells is essential for the structural integrity of the islets of Langerhans and maintenance of glucose homeostasis.

Authors:
M. Fuetterer 1,2 ; N. Chhabra 1,2 ; M. Irmler 1,2 ; J. Beckers 1,2,3 ; G. Przemeck 1,2 ; M. Hrabě de Angelis 1,2,3


Institutes
1) Institute of Experimental Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; 2) German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; 3) Chair of Experimental Genetics, Center of Life and Food Sciences, Weihenstephan, Technische Universität München, Freising, Germany.


Abstract:

The Notch signaling pathway is a short-range communication transducer involved in the regulation of many cellular processes. Genes of the pathway are expressed in different cell types and organs at different time points during embryonic development and adulthood. For example, the Notch ligand delta-like 1 (DLL1) controls the decision between endocrine and exocrine fates of progenitor stem cells in the developing pancreas; and loss of Dll1 function leads to premature differentiation of the pancreatic endocrine cell lineage. The ligands DLL1 and DLL4 as well as other members of the pathway are also expressed in the adult pancreas. However, the role of Notch signaling in adult tissue homeostasis is not well understood. Here, we describe cell-type specific, distinct expression of Notch pathway members in the adult murine pancreas. Using ligand-specific conditional loss- and gain-of-function mouse models we demonstrate alterations in islet morphology and effects on blood-glucose regulation as well as other metabolic parameters. Hence, we provide a first impression on functional aspects of Notch signaling in the adult islet and its importance for maintenance of tissue homeostasis.