ArticleAging cell2011
The Shc locus regulates insulin signaling and adiposity in mammals.
Article in Aging cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Small Molecule Insulin Sensitisers: New Leads and Targets for Next-Generation Insulin Sensitising Strategies.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- An illustrative summary of receptor-mediated mechanisms involved in the therapeutic regulation of type 2 diabetes.Hormones (Athens, Greece) · 2026Review
- P46Shc Inhibits Mitochondrial ACAA2 Thiolase, Exacerbating Mitochondrial Injury and Inflammation in Aging Livers.The American journal of pathology · 2025Article
- Acetylation in Cardiac Aging: Molecular Mechanism and Therapeutic Approaches.Results and problems in cell differentiation · 2025Review
- 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
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- The Role of p66Shc in Diabetes: A Comprehensive Review from Bench to Bedside.Journal of diabetes research · 2022Review
- Human SHC-transforming protein 1 and its isoforms p66shc: A novel marker for prediabetes.Journal of diabetes investigation · 2021Article
- Nonphagocytic Activation of NOX2 Is Implicated in Progressive Nonalcoholic Steatohepatitis During Aging.Hepatology (Baltimore, Md.) · 2020Article
- Article
- Modulation of Obesity and Insulin Resistance by the Redox Enzyme and Adaptor Protein p66International journal of molecular sciences · 2019Review
- Shc and the mechanotransduction of cellular anchorage and metastasis.Small GTPases · 2019Review
- Role of adaptor protein p66Shc in renal pathologies.American journal of physiology. Renal physiology · 2018Review
- The influence of Shc proteins and high-fat diet on energy metabolism of mice.Cell biochemistry and function · 2017Article
- Role of p66shc in skeletal muscle function.Scientific reports · 2017Article
- Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution: Part 3 of a 3-Part Series.Journal of the American College of Cardiology · 2017Review
- New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases.British journal of pharmacology · 2017Review
- Mice with low levels of Shc proteins display reduced glycolytic and increased gluconeogenic activities in liver.Biochemistry and biophysics reports · 2016Article
- p46Shc Inhibits Thiolase and Lipid Oxidation in Mitochondria.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Longevity of a p66Shc knockout strain (ShcP) was previously attributed to increased stress resistance and altered mitochondria. Microarrays of ShcP tissues indicated alterations in insulin signaling. Consistent with this observation, ShcP mice were more insulin sensitive and glucose tolerant at organismal and tissue levels, as was a novel p66Shc knockout (ShcL). Increasing and decreasing Shc expression in cell lines decreased and increased insulin sensitivity, respectively - consistent with p66Shc's function as a repressor of insulin signaling. However, differences between the two p66Shc knockout strains were also observed. ShcL mice were fatter and susceptible to fatty diets, and their fat was more insulin sensitive than controls. On the other hand, ShcP mice were leaner and resisted fatty diets, and their adipose was less insulin sensitive than controls. ShcL and ShcP strains are both highly inbred on the C57Bl/6 background, so we investigated gene expression at the Shc locus, which encodes three isoforms, p66, p52, and p46. Isoform p66 is absent in both strains; thus, the remaining difference to which to attribute the 'lean' phenotype is expression of the other two isoforms. ShcL mice have a precise deletion of p66Shc and normal expression of p52 and p46Shc isoforms in all tissues; thus, a simple deletion of p66Shc results in a 'fat' phenotype. However, ShcP mice in addition to p66Shc deletion have a fourfold increase in p46Shc expression in white fat. Thus, p46Shc overexpression in fat, rather than p66Shc deletion, is the likely cause of decreased adiposity and reduced insulin sensitivity in the fat of ShcP mice, which has implications for the longevity of the strain.
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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 OpenQuestion graph.