| First Author | Ardestani A | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5015 |
| PubMed ID | 31676778 | Mgi Jnum | J:282218 |
| Mgi Id | MGI:6378094 | Doi | 10.1038/s41467-019-12880-5 |
| Citation | Ardestani A, et al. (2019) Neratinib protects pancreatic beta cells in diabetes. Nat Commun 10(1):5015 |
| abstractText | The loss of functional insulin-producing beta-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic beta-cell death and dysfunction; its deficiency restores functional beta-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a beta-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves beta-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves beta-cell function, survival and beta-cell mass in type 1 (streptozotocin) and type 2 (obese Lepr(db/db)) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential beta-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes. |
