ArticleThe Journal of biological chemistry2016
Hyperactivation of the Insulin Signaling Pathway Improves Intracellular Proteostasis by Coordinately Up-regulating the Proteostatic Machinery in Adipocytes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Systems genetics approaches for understanding complex traits with relevance for human disease.eLife · 2023Review
- Article
- Inhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes.Scientific reports · 2022Article
- Carrying Excess Baggage Can Slowdown Life: Protein Clearance Machineries That Go Awry During Aging and the Relevance of Maintaining Them.Molecular neurobiology · 2022Review
- Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.International journal of molecular sciences · 2021Review
- Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity ineLife · 2021Article
- Build-UPS and break-downs: metabolism impacts on proteostasis and aging.Cell death and differentiation · 2021Review
- Fumarate and oxidative stress synergize to promote stability of C/EBP homologous protein in the adipocyte.Free radical biology & medicine · 2020Article
- Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes.Adipocyte · 2019Article
- Succination of Protein Disulfide Isomerase Links Mitochondrial Stress and Endoplasmic Reticulum Stress in the Adipocyte During Diabetes.Antioxidants & redox signaling · 2017Article
- Insulin Regulation of Proteostasis and Clinical Implications.Cell metabolism · 2017Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperinsulinemia, which is associated with aging and metabolic disease, may lead to defective protein homeostasis (proteostasis) due to hyperactivation of insulin-sensitive pathways such as protein synthesis. We investigated the effect of chronic hyperinsulinemia on proteostasis by generating a time-resolved map of insulin-regulated protein turnover in adipocytes using metabolic pulse-chase labeling and high resolution mass spectrometry. Hyperinsulinemia increased the synthesis of nearly half of all detected proteins and did not affect protein degradation despite suppressing autophagy. Unexpectedly, this marked elevation in protein synthesis was accompanied by enhanced protein stability and folding and not by markers of proteostasis stress such as protein carbonylation and aggregation. The improvement in proteostasis was attributed to a coordinate up-regulation of proteins in the global proteostasis network, including ribosomal, proteasomal, chaperone, and endoplasmic reticulum/mitochondrial unfolded protein response proteins. We conclude that defects associated with hyperactivation of the insulin signaling pathway are unlikely attributed to defective proteostasis because up-regulation of protein synthesis by insulin is accompanied by up-regulation of proteostatic machinery.
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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.