| First Author | Ruiz-Otero N | Year | 2023 |
| Journal | Front Endocrinol (Lausanne) | Volume | 14 |
| Pages | 1161085 | PubMed ID | 37223028 |
| Mgi Jnum | J:337239 | Mgi Id | MGI:7484928 |
| Doi | 10.3389/fendo.2023.1161085 | Citation | Ruiz-Otero N, et al. (2023) Role of Delta/Notch-like EGF-related receptor in blood glucose homeostasis. Front Endocrinol (Lausanne) 14:1161085 |
| abstractText | Cell-cell interactions are necessary for optimal endocrine functions in the pancreas. beta-cells, characterized by the expression and secretion of the hormone insulin, are a major constituent of functional micro-organs in the pancreas known as islets of Langerhans. Cell-cell contacts between beta-cells are required to regulate insulin production and glucose-stimulated insulin secretion, which are key determinants of blood glucose homeostasis. Contact-dependent interactions between beta-cells are mediated by gap junctions and cell adhesion molecules such as E-cadherin and N-CAM. Recent genome-wide studies have implicated Delta/Notch-like EGF-related receptor (Dner) as a potential susceptibility locus for Type 2 Diabetes in humans. DNER is a transmembrane protein and a proposed Notch ligand. DNER has been implicated in neuron-glia development and cell-cell interactions. Studies herein demonstrate that DNER is expressed in beta-cells with an onset during early postnatal life and sustained throughout adulthood in mice. DNER loss in adult beta-cells in mice (beta-Dner cKO mice) disrupted islet architecture and decreased the expression of N-CAM and E-cadherin. beta-Dner cKO mice also exhibited impaired glucose tolerance, defects in glucose- and KCl-induced insulin secretion, and decreased insulin sensitivity. Together, these studies suggest that DNER plays a crucial role in mediating islet cell-cell interactions and glucose homeostasis. |
