| Autor: |
Ghimire, Kedar, Kale, Atharva, Li, Jennifer, Julovi, Sohel M., O'Connell, Philip, Grey, Shane T., Hawthorne, Wayne J., Gunton, Jenny E., Rogers, Natasha M. |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 10/11/2023, Vol. 15 Issue 717, p1-14, 14p |
| Abstrakt: |
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 β 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 β 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 β cells offers a therapeutic opportunity for diabetes and islet transplantation by correcting insulin deficiency. Editor's summary: The cell surface glycoprotein CD47 is commonly understood as an immune-evasive "don't eat me" signal. Ghimire et al. now report that CD47 also limits insulin secretion by human and mouse pancreatic beta cells. Reducing CD47 improved glucose homeostasis and insulin sensitivity in an in vivo model of streptozotocin-induced diabetes and delayed disease onset and reduced disease severity in a model of autoimmune diabetes. Blocking islet CD47 with an antibody before syngeneic transplantation also improved graft survival and function, illustrating potential therapeutic relevance for type 1 diabetes. —Catherine Charneski [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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