RT Journal Article
T1 GATA6 Controls Insulin Biosynthesis and Secretion in Adult β-Cells.
A1 Villamayor, Laura
A1 Rodríguez-Seguel, Elisa
A1 Araujo, Raquel
A1 Carrasco, Manuel
A1 Bru-Tarí, Eva
A1 Mellado-Gil, José Manuel
A1 Gauthier, Benoit R
A1 Martinelli, Paola
A1 Quesada, Iván
A1 Soria, Bernat
A1 Martín, Franz
A1 Cano, David A
A1 Rojas, Anabel
AB GATA4 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.
YR 2017
FD 2017-12-20
LK http://hdl.handle.net/10668/11930
UL http://hdl.handle.net/10668/11930
LA en
DS RISalud
RD Apr 7, 2025