| First Author | Xiao X | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 8 | Pages | 3456-3465 |
| PubMed ID | 28057752 | Mgi Jnum | J:241086 |
| Mgi Id | MGI:5897713 | Doi | 10.1074/jbc.M116.770032 |
| Citation | Xiao X, et al. (2017) Forkhead Box Protein 1 (FoxO1) Inhibits Accelerated beta Cell Aging in Pancreas-specific SMAD7 Mutant Mice. J Biol Chem 292(8):3456-3465 |
| abstractText | The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in beta cell dysfunction with accelerated glucose intolerance, followed by overt diabetes. The accelerated beta cell dysfunction and loss of proliferation capacity, two features of beta cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a "bystander effect." Increased Forkhead box protein 1 (FoxO1) acetylation and nuclear retention was followed by progressive FoxO1 loss in beta cells that marked the onset of diabetes. Moreover, forced FoxO1 expression in beta cells prevented beta cell dysfunction and loss in this model. Thus, we present a model of accelerated beta cell aging that may be useful for studying the mechanisms underlying beta cell failure in diabetes. Moreover, we provide evidence highlighting a critical role of FoxO1 in maintaining beta cell identity in the context of SMAD7 failure. |
