ArticleThe Journal of biological chemistry2014
Pancreatic and duodenal homeobox protein 1 (Pdx-1) maintains endoplasmic reticulum calcium levels through transcriptional regulation of sarco-endoplasmic reticulum calcium ATPase 2b (SERCA2b) in the islet β cell.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- Review
- Sodium butyrate prevents cytokine-induced β-cell dysfunction through restoration of stromal interaction molecule 1 expression and activation of store-operated calcium entry.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- PDX1, a transcription factor essential for organ differentiation, regulates SERCA-dependent CaCell calcium · 2024Article
- The Ailing β-Cell in Diabetes: Insights From a Trip to the ER: The 2023 Outstanding Scientific Achievement Award Lecture.Diabetes · 2024Review
- Trimethylamine N-oxide impairs β-cell function and glucose tolerance.Nature communications · 2024Article
- Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids.Current research in pharmacology and drug discovery · 2024Review
- SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.Diabetologia · 2023Article
- Vitamin K-dependent carboxylation regulates CaCell reports · 2023Article
- CaBiomedicines · 2023Review
- Simultaneous Measurement of Changes in Mitochondrial and Endoplasmic Reticulum Free Calcium in Pancreatic Beta Cells.Biosensors · 2023Article
- TRPM7 kinase is required for insulin production and compensatory islet responses during obesity.JCI insight · 2023Article
- The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function.Journal of molecular endocrinology · 2022Article
- ROS and Endoplasmic Reticulum Stress in Pulmonary Disease.Frontiers in pharmacology · 2022Review
- Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice.Frontiers in pharmacology · 2021Article
- Pathological β-Cell Endoplasmic Reticulum Stress in Type 2 Diabetes: Current Evidence.Frontiers in endocrinology · 2021Review
- Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress.The Journal of biological chemistry · 2020Article
- ER stress increases store-operated CaThe Journal of biological chemistry · 2020Article
- Myricetin Protects Against High Glucose-Induced β-Cell Apoptosis by Attenuating Endoplasmic Reticulum Stress via Inactivation of Cyclin-Dependent Kinase 5.Diabetes & metabolism journal · 2019Article
- Endoplasmic reticulum stress alters ryanodine receptor function in the murine pancreatic β cell.The Journal of biological chemistry · 2019Article
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Authors and funding
9 authors at 7 institutions in 4 countries.
Funding
Abstract
Although the pancreatic duodenal homeobox 1 (Pdx-1) transcription factor is known to play an indispensable role in β cell development and secretory function, recent data also implicate Pdx-1 in the maintenance of endoplasmic reticulum (ER) health. The sarco-endoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) gradient between the cytosol and ER lumen. In models of diabetes, our data demonstrated loss of β cell Pdx-1 that occurs in parallel with altered SERCA2b expression, whereas in silico analysis of the SERCA2b promoter revealed multiple putative Pdx-1 binding sites. We hypothesized that Pdx-1 loss under inflammatory and diabetic conditions leads to decreased SERCA2b levels and activity with concomitant alterations in ER health. To test this, siRNA-mediated knockdown of Pdx-1 was performed in INS-1 cells. The results revealed reduced SERCA2b expression and decreased ER Ca(2+), which was measured using fluorescence lifetime imaging microscopy. Cotransfection of human Pdx-1 with a reporter fused to the human SERCA2 promoter increased luciferase activity 3- to 4-fold relative to an empty vector control, and direct binding of Pdx-1 to the proximal SERCA2 promoter was confirmed by chromatin immunoprecipitation. To determine whether restoration of SERCA2b could rescue ER stress induced by Pdx-1 loss, Pdx1(+/-) mice were fed a high-fat diet. Isolated islets demonstrated an increased spliced-to-total Xbp1 ratio, whereas SERCA2b overexpression reduced the Xbp1 ratio to that of wild-type controls. Together, these results identify SERCA2b as a novel transcriptional target of Pdx-1 and define a role for altered ER Ca(2+) regulation in Pdx-1-deficient states.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.