| First Author | Ljubicic S | Year | 2015 |
| Journal | Cell Rep | Volume | 10 |
| Issue | 4 | Pages | 497-504 |
| PubMed ID | 25640178 | Mgi Jnum | J:222889 |
| Mgi Id | MGI:5645863 | Doi | 10.1016/j.celrep.2014.12.056 |
| Citation | Ljubicic S, et al. (2015) Phospho-BAD BH3 mimicry protects beta cells and restores functional beta cell mass in diabetes. Cell Rep 10(4):497-504 |
| abstractText | Strategies that simultaneously enhance the survival and glucose responsiveness of insulin-producing beta cells will greatly augment beta cell replacement therapies in type 1 diabetes (T1D). We show that genetic and pharmacologic mimetics of the phosphorylated BCL-2 homology 3 (BH3) domain of BAD impart beta-cell-autonomous protective effects in the face of stress stimuli relevant to beta cell demise in T1D. Importantly, these benefits translate into improved engraftment of donor islets in transplanted diabetic mice, increased beta cell viability in islet grafts, restoration of insulin release, and diabetes reversal. Survival of beta cells in this setting is not merely due to the inability of phospho-BAD to suppress prosurvival BCL-2 proteins but requires its activation of the glucose-metabolizing enzyme glucokinase. Thus, BAD phospho-BH3 mimetics may prove useful in the restoration of functional beta cell mass in diabetes. |
