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Title: GATA6 Controls Insulin Biosynthesis and Secretion in Adult β-Cells.
Authors: Villamayor, Laura
Rodríguez-Seguel, Elisa
Araujo, Raquel
Carrasco, Manuel
Bru-Tarí, Eva
Mellado-Gil, José Manuel
Gauthier, Benoit R
Martinelli, Paola
Quesada, Iván
Soria, Bernat
Martín, Franz
Cano, David A
Rojas, Anabel
metadata.dc.subject.mesh: Animals
Blood Glucose
Endoplasmic Reticulum Stress
GATA6 Transcription Factor
Gene Expression Regulation, Developmental
Genes, Reporter
Glucose Intolerance
Homeodomain Proteins
Insulin Secretion
Insulin-Secreting Cells
Mice, Knockout
Mice, Transgenic
Microscopy, Electron, Transmission
Organelle Biogenesis
Secretory Vesicles
Tissue Culture Techniques
Issue Date: 20-Dec-2017
Abstract: 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.
metadata.dc.identifier.doi: 10.2337/db17-0364
Appears in Collections:Producción 2020

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