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Endocrinol."],"abstract":"<jats:p>Cell-cell interactions are necessary for optimal endocrine functions in the pancreas. \u03b2-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 \u03b2-cells are required to regulate insulin production and glucose-stimulated insulin secretion, which are key determinants of blood glucose homeostasis. Contact-dependent interactions between \u03b2-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 <jats:italic>(Dner)<\/jats:italic> 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 \u03b2-cells with an onset during early postnatal life and sustained throughout adulthood in mice. DNER loss in adult \u03b2-cells in mice (\u03b2-Dner cKO mice) disrupted islet architecture and decreased the expression of N-CAM and E-cadherin. \u03b2-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.<\/jats:p>","DOI":"10.3389\/fendo.2023.1161085","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T04:54:42Z","timestamp":1683521682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of Delta\/Notch-like EGF-related receptor in blood glucose homeostasis"],"prefix":"10.3389","volume":"14","author":[{"given":"Nelmari","family":"Ruiz-Otero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rejji","family":"Kuruvilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwt123","article-title":"Predicting risk of type 2 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