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Título

GATA6 controls Insulin biosynthesis and secretion in Adult ß cell

AutorVillamayor Coronado, Laura CSIC ORCID; Rodríguez-Seguel, Elisa CSIC; Araujo Legido, Raquel CSIC ORCID; Carrasco, Manuel CSIC ORCID; Bru-Tarí, Eva; Mellado-Gil, José Manuel CSIC; Gauthier, Benoit R. CSIC ORCID; Martinelli, Paola; Quesada, Iván; Soria Escoms, Bernat CSIC ORCID; Martín, Franz CSIC ORCID; Cano González, David A. CSIC ORCID; Rojas, Anabel CSIC ORCID
Fecha de publicaciónmar-2018
EditorAmerican Diabetes Association
CitaciónDiabetes - American Diabetes Association 67(3): 448-460 (2018)
ResumenGATA4 and GATA6 play essential, but redundant, roles in pancreas formation in mice, and GATA6 mutations cause pancreatic agenesis in humans. GATA6 mutations have also recently been linked to adult-onset diabetes, with subclinical or no exocrine insufficiency, suggesting an important role for GATA6 in human β-cell physiology. To investigate the role of GATA6 in the adult endocrine pancreas, we generated mice in which Gata6 is specifically inactivated in the pancreas. These mice develop glucose intolerance. Islets deficient in GATA6 activity display decreased insulin content and impaired insulin secretion. Gata6-deficient β-cells exhibit ultrastructural abnormalities, including increased immature insulin granules, swollen mitochondria, and disorganized endoplasmic reticulum. We also demonstrate that Pdx1 expression in adult β-cells depends on GATA sites in transgenic reporter mice and that loss of GATA6 greatly affects β-cell–specific gene expression. These findings demonstrate the essential role of GATA6 in β-cell function
Versión del editorhttps://doi.org/10.2337/db17-0364
URIhttp://hdl.handle.net/10261/180251
DOI10.2337/db17-0364
ISSN0012-1797
E-ISSN1939-327X
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