ArticleDiabetologia2015
The p66(Shc) redox adaptor protein is induced by saturated fatty acids and mediates lipotoxicity-induced apoptosis in pancreatic beta cells.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Long-term stability of the triglyceride-glucose index in cancer patient Cohort.Scientific reports · 2026Article
- Exploring the Gut-Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders.International journal of molecular sciences · 2024Review
- The p66International journal of molecular sciences · 2023Review
- Type 2 Diabetes and Alzheimer's Disease: The Emerging Role of Cellular Lipotoxicity.Biomolecules · 2023Review
- Ferroptosis Signaling in Pancreatic β-Cells: Novel Insights & Therapeutic Targeting.International journal of molecular sciences · 2022Review
- Association of p53 with Neurodegeneration in Parkinson's Disease.Parkinson's disease · 2022Review
- The Role of p66Shc in Diabetes: A Comprehensive Review from Bench to Bedside.Journal of diabetes research · 2022Review
- CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting.Cells · 2021Review
- NADPH Oxidase (NOX) Targeting in Diabetes: A Special Emphasis on Pancreatic β-Cell Dysfunction.Cells · 2021Review
- Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2021Review
- Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity.Biomolecules · 2021Review
- The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond.Diabetes & metabolism journal · 2020Review
- Article
- Functional Role of p53 in the Regulation of Chemical-Induced Oxidative Stress.Oxidative medicine and cellular longevity · 2020Review
- Lipotoxicity andJournal of the Endocrine Society · 2019Review
- Article
- Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets.Scientific reports · 2017Article
- Reduced first-phase insulin secretion increases postprandial lipidemia in subjects with impaired glucose tolerance.BMJ open diabetes research & care · 2017Article
- Bone Marrow-Derived Stem Cells: a Mixed Blessing in the Multifaceted World of Diabetic Complications.Current diabetes reports · 2016Review
- Tanshinol Rescues the Impaired Bone Formation Elicited by Glucocorticoid Involved in KLF15 Pathway.Oxidative medicine and cellular longevity · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe role of the redox adaptor protein p66(Shc) as a potential mediator of saturated fatty acid (FA)-induced beta cell death was investigated.
methodsThe effects of the FA palmitate on p66(Shc) expression were evaluated in human and murine islets and in rat insulin-secreting INS-1E cells. p66(Shc) expression was also measured in islets from mice fed a high-fat diet (HFD) and from human donors with different BMIs. Cell apoptosis was quantified by two independent assays. The role of p66(Shc) was investigated using pancreatic islets from p66 (Shc-/-) mice and in INS-1E cells with knockdown of p66(Shc) or overexpression of wild-type and phosphorylation-defective p66(Shc). Production of reactive oxygen species (ROS) was evaluated by the dihydroethidium oxidation method.
resultsPalmitate induced a selective increase in p66(Shc) protein expression and phosphorylation on Ser(36) and augmented apoptosis in human and mouse islets and in INS-1E cells. Inhibiting the tumour suppressor protein p53 prevented both the palmitate-induced increase in p66(Shc) expression and beta cell apoptosis. Palmitate-induced apoptosis was abrogated in islets from p66 (Shc-/-) mice and following p66 (Shc) knockdown in INS-1E cells; by contrast, overexpression of p66(Shc), but not that of the phosphorylation-defective p66(Shc) mutant, enhanced palmitate-induced apoptosis. The pro-apoptotic effects of p66(Shc) were dependent upon its c-Jun N-terminal kinase-mediated phosphorylation on Ser(36) and associated with generation of ROS. p66(Shc) protein expression and function were also elevated in islets from HFD-fed mice and from obese/overweight cadaveric human donors. CONCLUSIONS/
interpretationp53-dependent augmentation of p66(Shc) expression and function represents a key signalling response contributing to beta cell apoptosis under conditions of lipotoxicity.
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