ArticleBiological research2019
Palmitic acid-induced lipotoxicity promotes a novel interplay between Akt-mTOR, IRS-1, and FFAR1 signaling in pancreatic β-cells.
Article in Biological research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Beyond Glucose: Palmitic Acid Influences VEGFA-VEGFR2 Angiogenic Signaling in Müller Glial Cells.International journal of molecular sciences · 2026Article
- Pharmacological Inhibition of Pyruvate Dehydrogenase Kinase 4 Enhances Insulin Sensitivity in Mouse Models of Diabetes and Obesity.Journal of obesity & metabolic syndrome · 2026Article
- Anti-cancer effect of palmitic acid against the endometrial cancer progression via inducing ferroptosis.Biochemistry and biophysics reports · 2026Article
- Association of lipidome with senility and the mediated effect of metabolites: A Mendelian randomization study.Medicine · 2025Article
- Protection Strategies Against Palmitic Acid-Induced Lipotoxicity in Metabolic Syndrome and Related Diseases.International journal of molecular sciences · 2025Review
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- Targeting mTOR Kinase with Natural Compounds: Potent ATP-Competitive Inhibition Through Enhanced Binding Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Organelle-Targeted Laurdans Measure Heterogeneity in Subcellular Membranes and Their Responses to Saturated Lipid Stress.ACS chemical biology · 2024Article
- mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.International journal of molecular sciences · 2024Review
- Article
- Organelle-targeted Laurdans measure heterogeneity in subcellular membranes and their responses to saturated lipid stress.bioRxiv : the preprint server for biology · 2024Article
- Edible traditional Chinese medicines improve type 2 diabetes by modulating gut microbiotal metabolites.Acta diabetologica · 2024Review
- Comparative efficacy, toxicity, and insulin-suppressive effects of simvastatin and pravastatin in fatty acid-challenged mouse insulinoma MIN6 β-cell model.Frontiers in endocrinology · 2024Article
- Notoginsenoside R1, a metabolite from Panax notoginseng (Burkill) F.H.Chen, stimulates insulin secretion through activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway.Frontiers in pharmacology · 2024Article
- Mitochondrial reprogramming in peripheral blood mononuclear cells of patients with glycogen storage disease type Ia.Genes & nutrition · 2023Article
- Metabolite profiles of diabetes mellitus and response to intervention in anti-hyperglycemic drugs.Frontiers in endocrinology · 2023Review
- Branched-Chain Amino Acids and Their Interactions With Lipid Metabolites for Increased Risk of Gestational Diabetes.The Journal of clinical endocrinology and metabolism · 2022Article
- Review
- Integrated Omics Analysis Reveals Alterations in the Intestinal Microbiota and Metabolites of Piglets After Starvation.Frontiers in microbiology · 2022Article
- Mechanism of GLP-1 Receptor Agonists-Mediated Attenuation of Palmitic Acid-Induced Lipotoxicity in L6 Myoblasts.BioMed research international · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFree fatty acid receptor 1 (FFAR1) is G-protein coupled receptor predominantly expressed in pancreatic β-cells that is activated by a variety of free fatty acids (FFAs). Once activated, it promotes glucose-stimulated insulin secretion (GSIS). However, increased levels of FFAs lead to lipotoxicity, inducing loss of β-cell function. FFAR1 plays a key role in the development of type 2 diabetes (T2D), and previous studies have indicated the importance of developing anti-diabetic therapies against FFAR1, although its role in the regulation of β-cell function remains unclear. The present study investigated the role of FFAR1 under lipotoxic conditions using palmitic acid (PA). The rat insulinoma 1 clone 832/13 (INS-1 832/13) cell line was used as a model as it physiologically resembles native pancreatic β-cells. Key players of the insulin signaling pathway, such as mTOR, Akt, IRS-1, and the insulin receptor (INSR1β), were selected as candidates to be analyzed under lipotoxic conditions.
resultsWe revealed that PA-induced lipotoxicity affected GSIS in INS-1 cells and negatively modulated the activity of both IRS-1 and Akt. Reduced phosphorylation of both IRS-1 S636/639 and Akt S473 was observed, in addition to decreased expression of both INSR1β and FFAR1. Moreover, transient knockdown of FFAR1 led to a reduction in IRS-1 mRNA expression and an increase in INSR1β mRNA. Finally, PA affected localization of FFAR1 from the cytoplasm to the perinucleus.
conclusionsIn conclusion, our study suggests a novel regulatory involvement of FFAR1 in crosstalk with mTOR-Akt and IRS-1 signaling in β-cells under lipotoxic conditions.
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Registered trials
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 Socratic graph.