| First Author | Hurley LD | Year | 2023 |
| Journal | Front Endocrinol (Lausanne) | Volume | 14 |
| Pages | 1170461 | PubMed ID | 37124760 |
| Mgi Jnum | J:342757 | Mgi Id | MGI:7470062 |
| Doi | 10.3389/fendo.2023.1170461 | Citation | Hurley LD, et al. (2023) Ormdl3 regulation of specific ceramides is dispensable for mouse beta-cell function and glucose homeostasis under obesogenic conditions. Front Endocrinol (Lausanne) 14:1170461 |
| abstractText | Chronic elevation of sphingolipids contributes to beta-cell failure. ORMDL3 has been identified as a key regulator of sphingolipid homeostasis, however, its function in pancreatic beta-cell pathophysiology remains unclear. Here, we generated a mouse model lacking Ormdl3 within pancreatic beta-cells (Ormdl3 (beta-/-)). We show that loss of beta-cell Ormdl3 does not alter glucose tolerance, insulin sensitivity, insulin secretion, islet morphology, or cellular ceramide levels on standard chow diet. When challenged with a high fat diet, while Ormdl3 (beta-/-) mice did not exhibit any alteration in metabolic parameters or islet architecture, lipidomics analysis revealed significantly higher levels of very long chain ceramides in their islets. Taken together, our results reveal that loss of Ormdl3 alone is not sufficient to impinge upon beta-cell function or whole-body glucose and insulin homeostasis, however, beta-cell-specific loss of Ormdl3 does significantly alter levels of specific sphingolipid species in islets upon high fat feeding. |
