Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo.
Proc Natl Acad Sci U S A
; 104(13): 5680-5, 2007 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-17372192
ABSTRACT
Obesity is a major factor central to the development of insulin resistance and type 2 diabetes. The identification and characterization of genes involved in regulation of adiposity, insulin sensitivity, and glucose uptake are key to the design and development of new drug therapies for this disease. In this study, we show that the polarity kinase Par-1b/MARK2 is required for regulating glucose metabolism in vivo. Mice null for Par-1b were lean, insulin hypersensitive, resistant to high-fat diet-induced weight gain, and hypermetabolic. (18)F-FDG microPET and hyperinsulinemic-euglycemic clamp analyses demonstrated increased glucose uptake into white and brown adipose tissue, but not into skeletal muscle of Par-1b null mice relative to wild-type controls. Taken together, these data indicate that Par-1b is a regulator of glucose metabolism and adiposity in the whole animal and may be a valuable drug target for the treatment of both type 2 diabetes and obesity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Tecido Adiposo
/
Regulação da Expressão Gênica
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
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Adiposidade
/
Insulina
/
Obesidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article