SAD-A kinase controls islet β-cell size and function as a mediator of mTORC1 signaling

Jia Nie, Xiaolei Liu, Brendan N. Lilley, Hai Zhang, Y. Albert Pan, Scot R. Kimball, Jun Zhang, Weiping Zhang, Li Wang, Leonard S. Jefferson, Joshua R. Sanes, Xiao Han, Yuguang Shi

Resultado de la investigación: Articlerevisión exhaustiva

30 Citas (Scopus)


The mammalian target of rapamycin (mTOR) plays an important role in controlling islet β-cell function. However, the underlying molecular mechanisms remain poorly elucidated. Synapses of amphids defective kinase-A (SAD-A) is a 5′ adenosine monophosphate-activated protein kinase-related protein kinase that is exclusively expressed in pancreas and brain. In this study, we investigated a role of the kinase in regulating pancreatic β-cell morphology and function as a mediator of mTOR complex 1 (mTORC1) signaling. We show that global SAD-A deletion leads to defective glucose-stimulated insulin secretion and petite islets, which are reminiscent of the defects in mice with global deletion of ribosomal protein S6 kinase 1, a downstream target of mTORC1. Consistent with these findings, selective deletion of SAD-A in pancreas decreased islet β-cell size, whereas SAD-A overexpression significantly increased the size of mouse insulinomas cell lines β-cells. In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet β-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Moreover, the 5′-untranslated region of SADA mRNA is highly structured and requires mTORC1 signaling for its translation initiation. Together, these findings identified SAD-A as a unique pancreas-specific effector protein of mTORC1 signaling.

Idioma originalEnglish (US)
Páginas (desde-hasta)13857-13862
Número de páginas6
PublicaciónProceedings of the National Academy of Sciences of the United States of America
EstadoPublished - 2013
Publicado de forma externa

ASJC Scopus subject areas

  • General


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