ArticleDiabetes2009
Involvement of Per-Arnt-Sim Kinase and extracellular-regulated kinases-1/2 in palmitate inhibition of insulin gene expression in pancreatic beta-cells.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- The Dark Side of Sphingolipids: Searching for Potential Cardiovascular Biomarkers.Biomolecules · 2023Review
- Progress in Research on the Alleviation of Glucose Metabolism Disorders in Type 2 Diabetes UsingNutrients · 2022Review
- Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance.Medicines (Basel, Switzerland) · 2021Article
- MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus.Biology · 2021Review
- Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2021Review
- Role of ceramides in the pathogenesis of diabetes mellitus and its complications.Journal of diabetes and its complications · 2021Review
- Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Article
- MicroRNA-34c acts as a bidirectional switch in the maturation of insulin-producing cells derived from mesenchymal stem cells.Oncotarget · 2017Article
- Involvement of receptor-interacting protein 140 in palmitate-stimulated macrophage infiltration of pancreatic beta cells.Experimental and therapeutic medicine · 2017Article
- Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2016Review
- Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production.Diabetologia · 2016Article
- Per-Arnt-Sim Kinase (PASK): An Emerging Regulator of Mammalian Glucose and Lipid Metabolism.Nutrients · 2015Review
- Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells.Frontiers in pharmacology · 2015Article
- SUMO1 enhances cAMP-dependent exocytosis and glucagon secretion from pancreatic α-cells.The Journal of physiology · 2014Article
- Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like receptor 4 signaling in diabetic nephropathy.Clinical and experimental nephrology · 2014Review
- A comprehensive protein-protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1.Molecular biology of the cell · 2014Article
- Roles of Sphingolipid Metabolism in Pancreatic β Cell Dysfunction Induced by Lipotoxicity.Journal of clinical medicine · 2014Review
- Article
- Transcription factor Ets1 regulates expression of thioredoxin-interacting protein and inhibits insulin secretion in pancreatic β-cells.PloS one · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveProlonged exposure of pancreatic beta-cells to simultaneously elevated levels of fatty acids and glucose (glucolipotoxicity) impairs insulin gene transcription. However, the intracellular signaling pathways mediating these effects are mostly unknown. This study aimed to ascertain the role of extracellular-regulated kinases (ERKs)1/2, protein kinase B (PKB), and Per-Arnt-Sim kinase (PASK) in palmitate inhibition of insulin gene expression in pancreatic beta-cells. RESEARCH DESIGN AND
methodsMIN6 cells and isolated rat islets were cultured in the presence of elevated glucose, with or without palmitate or ceramide. ERK1/2 phosphorylation, PKB phosphorylation, and PASK expression were examined by immunoblotting and real-time PCR. The role of these kinases in insulin gene expression was assessed using pharmacological and molecular approaches.
resultsExposure of MIN6 cells and islets to elevated glucose induced ERK1/2 and PKB phosphorylation, which was further enhanced by palmitate. Inhibition of ERK1/2, but not of PKB, partially prevented the inhibition of insulin gene expression in the presence of palmitate or ceramide. Glucose-induced expression of PASK mRNA and protein levels was reduced in the presence of palmitate. Overexpression of wild-type PASK increased insulin and pancreatic duodenal homeobox-1 gene expression in MIN6 cells and rat islets incubated with glucose and palmitate, whereas overexpression of a kinase-dead PASK mutant in rat islets decreased expression of insulin and pancreatic duodenal homeobox-1 and increased C/EBPbeta expression.
conclusionsBoth the PASK and ERK1/2 signaling pathways mediate palmitate inhibition of insulin gene expression. These findings identify PASK as a novel mediator of glucolipotoxicity on the insulin gene in pancreatic beta-cells.
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