ArticleDiabetologia2016
Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 98 citations in OpenAlex.
- Restoring Mitochondrial Homeostasis: Therapeutic Strategies for Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2026Review
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- A Compound Screen Based on Isogenic hESC-Derived β Cell Reveals an Inhibitor Targeting ZnT8-Mediated Zinc Transportation to Protect Pancreatic β Cell from Stress-Induced Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Impact of Olive Oil Components on the Expression of Genes Related to Type 2 Diabetes Mellitus.Nutrients · 2025Review
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid.Cellular and molecular life sciences : CMLS · 2024Article
- Comparison of the effects of monounsaturated fatty acids and polyunsaturated fatty acids on the lipotoxicity of islets.Frontiers in endocrinology · 2024Article
- A Review of micro RNAs changes in T2DM in animals and humans.Journal of diabetes · 2023Review
- Dissecting the effects of paraquat-induced pulmonary injury in rats using UPLC-Q-TOF-MS/MS-based metabonomics.Toxicology research · 2023Article
- Article
- Metabolome Profiling and Pathway Analysis in Metabolically Healthy and Unhealthy Obesity among Chinese Adolescents Aged 11-18 Years.Metabolites · 2023Article
- A comprehensive overview on Micro RNA signature in type 2 diabetes Mellitus and its complications.Indian journal of clinical biochemistry : IJCB · 2023Review
- Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk.Arquivos brasileiros de cardiologia · 2023Article
- Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes.Nature communications · 2022Article
- Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Untargeted sequencing of circulating microRNAs in a healthy and diseased older population.Scientific reports · 2022Article
- In silico functional and pathway analysis of risk genes and SNPs for type 2 diabetes in Asian population.PloS one · 2022Article
- Gallic Acid Improves Diabetic Steatosis by Downregulating MicroRNA-34a-5p through Targeting NFE2L2 Expression in High-Fat Diet-Fed db/db Mice.Antioxidants (Basel, Switzerland) · 2021Article
- Comparative analysis of circRNA expression profile and circRNA-miRNA-mRNA regulatory network between palmitic and stearic acid-induced lipotoxicity to pancreatic β cells.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisSerum stearic acid (C18:0) is elevated in individuals with hyperlipidaemia and type 2 diabetes. However, the lipotoxicity induced by increased stearic acid in beta cells has not been well described. This study aimed to examine the adverse effects of stearic acid on beta cells and the potential mechanisms through which these are mediated.
methodsThree groups of C57BL/6 mice were fed a normal diet or a high-stearic-acid/high-palmitic-acid diet for 24 weeks, respectively. The microRNA (miR) profiles of islets were determined by microarray screening. Islet injury was detected with co-staining using the TUNEL assay and insulin labelling. A lentiviral vector expressing anti-miRNA-34a-5p oligonucleotide (AMO-34a-5p) was injected into mice via an intraductal pancreatic route.
resultsIn both mouse islets and cultured rat insulinoma INS-1 cells, stearic acid exhibited a stronger lipotoxic role than other fatty acids, owing to repression of B cell CLL/lymphoma 2 (BCL-2) and BCL-2-like 2 (BCL-W) by stearic acid stimulation of miR-34a-5p. The stearic-acid-induced lipotoxicity and reduction in insulin secretion were alleviated by AMO-34a-5p. Further investigations in INS-1 cells revealed that p53 was involved in stearic-acid-induced elevation of miR-34a-5p, owing in part to activation of protein kinase-like endoplasmic reticulum kinase (PERK). Conversely, silencing PERK alleviated stearic-acid-induced p53, miR-34a-5p and lipotoxicity. CONCLUSIONS/
interpretationThese findings provide new insight for understanding the molecular mechanisms underlying not only the deleterious impact of stearic-acid-induced lipotoxicity but also apoptosis in beta cells and progression to type 2 diabetes.
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