Chronic Activation of γ2 AMPK Induces Obesity and Reduces ß Cell Function.
Cell Metab
; 23(5): 821-36, 2016 May 10.
Article
en En
| MEDLINE
| ID: mdl-27133129
ABSTRACT
Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Secretoras de Insulina
/
Proteínas Quinasas Activadas por AMP
/
Obesidad
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido