ArticleMolecular and cellular biochemistry2010
Blockage of ceramide metabolism exacerbates palmitate inhibition of pro-insulin gene expression in pancreatic beta-cells.
Article in Molecular and cellular biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Ceramide in Type 2 Diabetes and Obesity: Modulation by Nutrients and Dietary Patterns and Opportunities to Prevent and/or Manage Metabolic-Related Conditions.Metabolites · 2026Review
- A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.Frontiers in pharmacology · 2024Review
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- The Dark Side of Sphingolipids: Searching for Potential Cardiovascular Biomarkers.Biomolecules · 2023Review
- 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
- Temporal Proteomic Analysis of Pancreatic β-Cells in Response to Lipotoxicity and Glucolipotoxicity.Molecular & cellular proteomics : MCP · 2018Article
- Erythrocyte Saturated Fatty Acids and Incident Type 2 Diabetes in Chinese Men and Women: A Prospective Cohort Study.Nutrients · 2018Article
- Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and Causes β-Cell Impairment via Mitochondrial Dysregulation.Endocrinology and metabolism (Seoul, Korea) · 2018Article
- The role of sphingolipid signalling in diabetes‑associated pathologies (Review).International journal of molecular medicine · 2017Review
- Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2016Review
- p38 MAPK Is Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Acid in Human Pancreatic β-Cells.International journal of molecular sciences · 2016Article
- Reg3α Overexpression Protects Pancreatic β Cells from Cytokine-Induced Damage and Improves Islet Transplant Outcome.Molecular medicine (Cambridge, Mass.) · 2015Article
- Roles of Sphingolipid Metabolism in Pancreatic β Cell Dysfunction Induced by Lipotoxicity.Journal of clinical medicine · 2014Review
- Sphingolipid regulators of cellular dysfunction in Type 2 diabetes mellitus: a systems overview.Clinical lipidology · 2014Article
- Role of ceramide in diabetes mellitus: evidence and mechanisms.Lipids in health and disease · 2013Review
- Sphingolipids in obesity, type 2 diabetes, and metabolic disease.Handbook of experimental pharmacology · 2013Review
- Sphingosine 1-phosphate (S1P) regulates glucose-stimulated insulin secretion in pancreatic beta cells.The Journal of biological chemistry · 2012Article
- DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients.The EMBO journal · 2012Article
- Ceramides as modulators of cellular and whole-body metabolism.The Journal of clinical investigation · 2011Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic exposure to elevated levels of fatty acids (FAs) in conjunction with chronic hyperglycemia has been reported to contribute to the progressive deterioration of beta-cell function in patients with type 2 diabetes mellitus. The long-chain saturated free fatty acid (FFA) palmitate, unlike the unsaturated FFA oleate, is known to have an inhibitory effect on proinsulin gene expression through ceramide synthesis. This study was aimed at investigating whether this effect was exacerbated by the inhibition of ceramide degradation in pancreatic beta-cells and the molecular mechanism of intracellular ceramide-induced inhibition of proinsulin gene transcription in response to exposure to palmitate. We exposed insulin-secreting (INS-1) cells treated with low levels of palmitate to the ceramidase inhibitor n-oleoylethanolamine (NOE); this led to the generation of high levels of intracellular ceramide. We observed that the effects of ceramide accumulation in INS-1 cells were similar to the effects of the inhibition of this protein on proinsulin mRNA levels that are caused by the negative regulation of insulin promoter activity. In addition, we observed that ceramide accumulation induced by NOE leads to a significant decrease in the levels of activated extracellular signal-regulated kinase (ERK); the inactivation of the ERK cascade in response to palmitate stimuli is induced by protein phosphatase 2A (PP2A) activity. Based on these findings, we suggest that the aberrant accumulation of ceramide was caused by the inhibition of ceramide metabolism, which in turn leads to the inhibition of proinsulin gene expression; the inhibition of ERK cascades by PP2A serves as an important factor in the inhibitory effects of ceramide.
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