| First Author | Ghimire K | Year | 2023 |
| Journal | Sci Transl Med | Volume | 15 |
| Issue | 717 | Pages | eadd2387 |
| PubMed ID | 37820008 | Mgi Jnum | J:343752 |
| Mgi Id | MGI:7567559 | Doi | 10.1126/scitranslmed.add2387 |
| Citation | Ghimire K, et al. (2023) A metabolic role for CD47 in pancreatic beta cell insulin secretion and islet transplant outcomes. Sci Transl Med 15(717):eadd2387 |
| abstractText | Diabetes is a global public health burden and is characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate insulin secretion and improve insulin sensitivity are in high demand as treatment options. CD47 is a cell surface glycoprotein implicated in multiple cellular functions including recognition of self, angiogenesis, and nitric oxide signaling; however, its role in the regulation of insulin secretion remains unknown. Here, we demonstrate that CD47 receptor signaling inhibits insulin release from human as well as mouse pancreatic beta cells and that it can be pharmacologically exploited to boost insulin secretion in both models. CD47 depletion stimulated insulin granule exocytosis via activation of the Rho GTPase Cdc42 in beta cells and improved glucose clearance and insulin sensitivity in vivo. CD47 blockade enhanced syngeneic islet transplantation efficiency and expedited the return to euglycemia in streptozotocin-induced diabetic mice. Further, anti-CD47 antibody treatment delayed the onset of diabetes in nonobese diabetic (NOD) mice and protected them from overt diabetes. Our findings identify CD47 as a regulator of insulin secretion, and its manipulation in beta cells offers a therapeutic opportunity for diabetes and islet transplantation by correcting insulin deficiency. |
