Phospho-BAD BH3 Mimicry Protects β Cells and Restores Functional β Cell Mass in Diabetes
| Autor: | Nika N. Danial, Yigang Chang, Adolfo Garcia-Ocaña, Loren D. Walensky, Sanda Ljubicic, Accalia Fu, Gregory H. Bird, Klaudia Polak, Jessica Wiwczar, Benjamin Szlyk, Juan Carlos Alvarez-Perez |
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| Rok vydání: | 2015 |
| Předmět: |
inorganic chemicals
medicine.medical_specialty Cell Survival medicine.medical_treatment Cell 030209 endocrinology & metabolism macromolecular substances In Vitro Techniques Biology environment and public health Article General Biochemistry Genetics and Molecular Biology Cell Line Diabetes Mellitus Experimental Mice 03 medical and health sciences 0302 clinical medicine Insulin-Secreting Cells Internal medicine Diabetes mellitus Glucokinase medicine Animals Viability assay lcsh:QH301-705.5 Cells Cultured 030304 developmental biology 0303 health sciences Type 1 diabetes geography geography.geographical_feature_category Insulin medicine.disease Islet Rats 3. Good health Cell biology enzymes and coenzymes (carbohydrates) Endocrinology medicine.anatomical_structure lcsh:Biology (General) bacteria Phosphorylation bcl-Associated Death Protein |
| Zdroj: | Cell Reports, Vol 10, Iss 4, Pp 497-504 (2015) |
| ISSN: | 2211-1247 |
| Popis: | SummaryStrategies that simultaneously enhance the survival and glucose responsiveness of insulin-producing β cells will greatly augment β 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 β-cell-autonomous protective effects in the face of stress stimuli relevant to β cell demise in T1D. Importantly, these benefits translate into improved engraftment of donor islets in transplanted diabetic mice, increased β cell viability in islet grafts, restoration of insulin release, and diabetes reversal. Survival of β 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 β cell mass in diabetes. |
| Databáze: | OpenAIRE |
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