| First Author | Oh E | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 12 | Pages | 2626-2639 |
| PubMed ID | 30305365 | Mgi Jnum | J:267773 |
| Mgi Id | MGI:6258151 | Doi | 10.2337/db18-0259 |
| Citation | Oh E, et al. (2018) Syntaxin 4 Expression in Pancreatic beta-Cells Promotes Islet Function and Protects Functional beta-Cell Mass. Diabetes 67(12):2626-2639 |
| abstractText | Syntaxin 4 (Stx4) enrichment in human and mouse islet grafts improves the success of transplants in reversing streptozotocin (STZ)-induced diabetes in mice, although the underlying molecular mechanisms remain elusive. Toward a further understanding of this, human islets and inducible transgenic mice that selectively overexpress Stx4 in islet beta-cells (betaTG-Stx4) were challenged with proinflammatory stressors in vitro and in vivo. Remarkably, betaTG-Stx4 mice resisted the loss of beta-cell mass and the glucose intolerance that multiple low doses of STZ induce. Under standard conditions, glucose tolerance was enhanced and mice maintained normal fasting glycemia and insulinemia. Conversely, Stx4 heterozygous knockout mice succumbed rapidly to STZ-induced glucose intolerance compared with their wild-type littermates. Human islet beta-cells overexpressing Stx4 exhibited enhanced insulin secretory capability; resilience against proinflammatory cytokine-induced apoptosis; and reduced expression of the CXCL9, CXCL10, and CXCL11 genes coordinate with decreased activation/nuclear localization of nuclear factor-kappaB. Finding ways to boost Stx4 expression presents a novel potential therapeutic avenue for promoting islet function and preserving beta-cell mass. |
