| First Author | Wang Z | Year | 2014 |
| Journal | Cell Metab | Volume | 19 |
| Issue | 5 | Pages | 872-82 |
| PubMed ID | 24746806 | Mgi Jnum | J:214774 |
| Mgi Id | MGI:5603987 | Doi | 10.1016/j.cmet.2014.03.010 |
| Citation | Wang Z, et al. (2014) Pancreatic beta cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab 19(5):872-82 |
| abstractText | Diabetes is characterized by "glucotoxic" loss of pancreatic beta cell function and insulin content, but underlying mechanisms remain unclear. A mouse model of insulin-secretory deficiency induced by beta cell inexcitability (K(ATP) gain of function) demonstrates development of diabetes and reiterates the features of human neonatal diabetes. In the diabetic state, beta cells lose their mature identity and dedifferentiate to neurogenin3-positive and insulin-negative cells. Lineage-tracing experiments show that dedifferentiated cells can subsequently redifferentiate to mature neurogenin3-negative, insulin-positive beta cells after lowering of blood glucose by insulin therapy. We demonstrate here that beta cell dedifferentiation, rather than apoptosis, is the main mechanism of loss of insulin-positive cells, and redifferentiation accounts for restoration of insulin content and antidiabetic drug responsivity in these animals. These results may help explain gradual decrease in beta cell mass in long-standing diabetes and recovery of beta cell function and drug responsivity in type 2 diabetic patients following insulin therapy, and they suggest an approach to rescuing "exhausted" beta cells in diabetes. |
