| First Author | Watanabe H | Year | 2024 |
| Journal | PLoS One | Volume | 19 |
| Issue | 2 | Pages | e0297555 |
| PubMed ID | 38335173 | Mgi Jnum | J:351015 |
| Mgi Id | MGI:7594963 | Doi | 10.1371/journal.pone.0297555 |
| Citation | Watanabe H, et al. (2024) Cyb5r3 activation rescues secondary failure to sulfonylurea but not beta-cell dedifferentiation. PLoS One 19(2):e0297555 |
| abstractText | Diabetes mellitus is characterized by insulin resistance and beta-cell failure. The latter involves impaired insulin secretion and beta-cell dedifferentiation. Sulfonylurea (SU) is used to improve insulin secretion in diabetes, but it suffers from secondary failure. The relationship between SU secondary failure and beta-cell dedifferentiation has not been examined. Using a model of SU secondary failure, we have previously shown that functional loss of oxidoreductase Cyb5r3 mediates effects of SU failure through interactions with glucokinase. Here we demonstrate that SU failure is associated with partial beta-cell dedifferentiation. Cyb5r3 knockout mice show more pronounced beta-cell dedifferentiation and glucose intolerance after chronic SU administration, high-fat diet feeding, and during aging. A Cyb5r3 activator improves impaired insulin secretion caused by chronic SU treatment, but not beta-cell dedifferentiation. We conclude that chronic SU administration affects progression of beta-cell dedifferentiation and that Cyb5r3 activation reverses secondary failure to SU without restoring beta-cell dedifferentiation. |
