ArticleDiabetologia2020
Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Human β-Cell Dedifferentiation and Diabetes.Journal of diabetes · 2026Review
- Compositional recalibrations of cardiolipin integrate loss of stearoyl-CoA desaturase 1 activity with mitochondrial decay in lipid-laden pancreatic β-cells.Cell communication and signaling : CCS · 2026Article
- Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Gain of pancreatic beta cell-specific SCD1 improves glucose homeostasis by maintaining functional beta cell mass under metabolic stress.Diabetologia · 2025Article
- High expression of stearoyl-coenzyme A desaturase in colorectal cancer oncogenic functions and its potential as a therapeutic target.World journal of gastrointestinal surgery · 2025Article
- A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response.Experimental & molecular medicine · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Comparison of the effects of monounsaturated fatty acids and polyunsaturated fatty acids on the lipotoxicity of islets.Frontiers in endocrinology · 2024Article
- Unmasking metabolic disruptors: The NEMESIS project's quest for Novel Biomarkers, Evidence on Adverse Effects, and Efficient Methodologies.Open research Europe · 2024Article
- Impact of Chromium Picolinate on Leydig Cell Steroidogenesis and Antioxidant Balance Using an In Vitro Insulin Resistance Model.Antioxidants (Basel, Switzerland) · 2023Article
- Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients.Nutrients · 2023Review
- Type 2 Diabetes and Alzheimer's Disease: The Emerging Role of Cellular Lipotoxicity.Biomolecules · 2023Review
- Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis.Nature cell biology · 2023Article
- Mining the transcriptome of target tissues of autoimmune and degenerative pancreatic β-cell and brain diseases to discover therapies.iScience · 2022Article
- Differential routing and disposition of the long-chain saturated fatty acid palmitate in rodent vs human beta-cells.Nutrition & diabetes · 2022Article
- Article
- Lipid Droplets' Role in the Regulation of β-Cell Function and β-Cell Demise in Type 2 Diabetes.Endocrinology · 2022Review
- To Be or Not to Be: The Divergent Action and Metabolism of Sphingosine-1 Phosphate in Pancreatic Beta-Cells in Response to Cytokines and Fatty Acids.International journal of molecular sciences · 2022Review
- Large-Scale Functional Genomics Screen to Identify Modulators of Human β-Cell Insulin Secretion.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
15 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisDuring the onset of type 2 diabetes, excessive dietary intake of saturated NEFA and fructose lead to impaired insulin production and secretion by insulin-producing pancreatic beta cells. The majority of data on the deleterious effects of lipids on functional beta cell mass were obtained either in vivo in rodent models or in vitro using rodent islets and beta cell lines. Translating data from rodent to human beta cells remains challenging. Here, we used the human beta cell line EndoC-βH1 and analysed its sensitivity to a lipotoxic and glucolipotoxic (high palmitate with or without high glucose) insult, as a way to model human beta cells in a type 2 diabetes environment.
methodsEndoC-βH1 cells were exposed to palmitate after knockdown of genes related to saturated NEFA metabolism. We analysed whether and how palmitate induces apoptosis, stress and inflammation and modulates beta cell identity.
resultsEndoC-βH1 cells were insensitive to the deleterious effects of saturated NEFA (palmitate and stearate) unless stearoyl CoA desaturase (SCD) was silenced. SCD was abundantly expressed in EndoC-βH1 cells, as well as in human islets and human induced pluripotent stem cell-derived beta cells. SCD silencing induced markers of inflammation and endoplasmic reticulum stress and also IAPP mRNA. Treatment with the SCD products oleate or palmitoleate reversed inflammation and endoplasmic reticulum stress. Upon SCD knockdown, palmitate induced expression of dedifferentiation markers such as SOX9, MYC and HES1. Interestingly, SCD knockdown by itself disrupted beta cell identity with a decrease in mature beta cell markers INS, MAFA and SLC30A8 and decreased insulin content and glucose-stimulated insulin secretion. CONCLUSIONS/
interpretationThe present study delineates an important role for SCD in the protection against lipotoxicity and in the maintenance of human beta cell identity. DATA AVAILABILITY: Microarray data and all experimental details that support the findings of this study have been deposited in in the GEO database with the GSE130208 accession code.
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