| First Author | Zhang X | Year | 2022 |
| Journal | Dev Cell | Volume | 57 |
| Issue | 12 | Pages | 1496-1511.e6 |
| PubMed ID | 35675813 | Mgi Jnum | J:342800 |
| Mgi Id | MGI:7295287 | Doi | 10.1016/j.devcel.2022.05.013 |
| Citation | Zhang X, et al. (2022) IL18 signaling causes islet beta cell development and insulin secretion via different receptors on acinar and beta cells. Dev Cell 57(12):1496-1511.e6 |
| abstractText | Diabetic patients show elevated plasma IL18 concentrations. IL18 has two receptors: the IL18 receptor (IL18r) and the Na-Cl co-transporter (NCC). Here, we report that IL18 is expressed on islet alpha cells, NCC on beta cells, and IL18r on acinar cells in human and mouse pancreases. The deficiency of these receptors reduces islet size, beta cell proliferation, and insulin secretion but increases beta cell apoptosis and exocrine macrophage accumulation after diet-induced glucose intolerance or streptozotocin-induced hyperglycemia. Together with the glucagon-like peptide-1 (GLP1), IL18 uses the NCC and GLP1 receptors on beta cells to trigger beta cell development and insulin secretion. IL18 also uses the IL18r on acinar cells to block hyperglycemic pancreas macrophage expansion. The beta cell-selective depletion of the NCC or acinar-cell-selective IL18r depletion reduces glucose tolerance and insulin sensitivity with impaired beta cell proliferation, enhanced beta cell apoptosis and macrophage expansion, and inflammation in mouse hyperglycemic pancreas. IL18 uses NCC, GLP1r, and IL18r to maintain islet beta cell function and homeostasis. |
