Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Diabetes ; 68(11): 2049-2062, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31439647

RESUMO

Disruption of the adaptor protein SH2B1 (SH2-B, PSM) is associated with severe obesity, insulin resistance, and neurobehavioral abnormalities in mice and humans. Here, we identify 15 SH2B1 variants in severely obese children. Four obesity-associated human SH2B1 variants lie in the Pleckstrin homology (PH) domain, suggesting that the PH domain is essential for SH2B1's function. We generated a mouse model of a human variant in this domain (P322S). P322S/P322S mice exhibited substantial prenatal lethality. Examination of the P322S/+ metabolic phenotype revealed late-onset glucose intolerance. To circumvent P322S/P322S lethality, mice containing a two-amino acid deletion within the SH2B1 PH domain (ΔP317, R318 [ΔPR]) were studied. Mice homozygous for ΔPR were born at the expected Mendelian ratio and exhibited obesity plus insulin resistance and glucose intolerance beyond that attributable to their increased adiposity. These studies demonstrate that the PH domain plays a crucial role in how SH2B1 controls energy balance and glucose homeostasis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adiposidade/genética , Metabolismo Energético/genética , Resistência à Insulina/genética , Obesidade Infantil/genética , Domínios de Homologia à Plecstrina/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Homeostase/genética , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Obesidade Infantil/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...