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.
Nat Commun ; 14(1): 235, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646689

RESUMO

Glucagon has emerged as a key regulator of extracellular amino acid (AA) homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Aside from mammalian target of rapamycin complex 1 (mTORC1), the role of other AA sensors in α cell proliferation has not been described. Here, using both genders of mouse islets and glucagon receptor (gcgr)-deficient zebrafish (Danio rerio), we show α cell proliferation requires activation of the extracellular signal-regulated protein kinase (ERK1/2) by the AA-sensitive calcium sensing receptor (CaSR). Inactivation of CaSR dampened α cell proliferation, which was rescued by re-expression of CaSR or activation of Gq, but not Gi, signaling in α cells. CaSR was also unexpectedly necessary for mTORC1 activation in α cells. Furthermore, coactivation of Gq and mTORC1 induced α cell proliferation independent of hyperaminoacidemia. These results reveal another AA-sensitive mediator and identify pathways necessary and sufficient for hyperaminoacidemia-induced α cell proliferation.


Assuntos
Células Secretoras de Glucagon , Alvo Mecanístico do Complexo 1 de Rapamicina , Receptores de Detecção de Cálcio , Transdução de Sinais , Animais , Feminino , Masculino , Camundongos , Cálcio/metabolismo , Proliferação de Células , Glucagon , Células Secretoras de Glucagon/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Peixe-Zebra/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA