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MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
- Source :
-
Diabetes . Mar2018, Vol. 67 Issue 3, p461-472. 12p. - Publication Year :
- 2018
-
Abstract
- Although the mechanisms by which glucose regulates insulin secretion from pancreatic β-cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralog carbohydrate-responsive element-binding protein, is the predominant glucose-responsive transcription factor in human pancreatic β-EndoC-βH1 cells and in human islets. In high-glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes arrestin domain-containing protein 4 (ARRDC4) and thioredoxin interacting protein (TXNIP), the latter being a protein strongly linked to β-cell dysfunction and diabetes. Importantly, increasing cAMP signaling in human β-cells, using forskolin or the glucagon-like peptide 1 mimetic Exendin-4, inhibits the shuttling of MondoA and potently inhibits TXNIP and ARRDC4 expression. Furthermore, we demonstrate that silencing MondoA expression improves glucose uptake in EndoC-βH1 cells. These results highlight MondoA as a novel target in β-cells that coordinates transcriptional response to elevated glucose levels. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PROTEIN metabolism
*GLUCOSE metabolism
*ANIMAL experimentation
*BIOLOGICAL transport
*CARRIER proteins
*CELL lines
*CELLULAR signal transduction
*COMPARATIVE studies
*CYCLIC adenylic acid
*GENES
*INSULIN
*ISLANDS of Langerhans
*RESEARCH methodology
*INCRETINS
*MEDICAL cooperation
*MICE
*PEPTIDES
*PROTEINS
*RESEARCH
*TISSUE culture
*VENOM
*EVALUATION research
*SIGNAL peptides
*CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 67
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 128134119
- Full Text :
- https://doi.org/10.2337/db17-0595