Acceleration of ß Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes.
Cell Metab
; 30(1): 129-142.e4, 2019 07 02.
Article
em En
| MEDLINE
| ID: mdl-31155496
ABSTRACT
Type 2 diabetes (T2D) is an age-related disease. Although changes in function and proliferation of aged ß cells resemble those preceding the development of diabetes, the contribution of ß cell aging and senescence remains unclear. We generated a ß cell senescence signature and found that insulin resistance accelerates ß cell senescence leading to loss of function and cellular identity and worsening metabolic profile. Senolysis (removal of senescent cells), using either a transgenic INK-ATTAC model or oral ABT263, improved glucose metabolism and ß cell function while decreasing expression of markers of aging, senescence, and senescence-associated secretory profile (SASP). Beneficial effects of senolysis were observed in an aging model as well as with insulin resistance induced both pharmacologically (S961) and physiologically (high-fat diet). Human senescent ß cells also responded to senolysis, establishing the foundation for translation. These novel findings lay the framework to pursue senolysis of ß cells as a preventive and alleviating strategy for T2D.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Glucose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article