ArticleThe Journal of endocrinology2010
Glycogen synthase kinase 3 beta mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1.
Article in The Journal of endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Coptidis Rhizoma for Obesity, Diabetes, and Dyslipidemia: An Integrated Meta-Analysis and In Silico Study.International journal of molecular sciences · 2026Pooled it
- Mechanobiology-Driven Metabolic Reprogramming: Integrative Roles of YAP/TAZ Signaling and Extracellular Matrix Dynamics.Cell biology international · 2026Review
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- MAD-microbial (origin of) Alzheimer's disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems.Frontiers in neuroscience · 2024Review
- The effect of hormones insulin and glucagon on ubiquitin modifications elucidated by proteomics in liver cells.Life sciences · 2023Article
- GSK-3 at the heart of cardiometabolic diseases: Isoform-specific targeting is critical to therapeutic benefit.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Article
- High-Intensity Interval Training Ameliorates Molecular Changes in the Hippocampus of Male Rats with the Diabetic Brain: the Role of Adiponectin.Molecular neurobiology · 2023Article
- Hepatocyte Toll-Like Receptor 4 Mediates Alcohol-Induced Insulin Resistance in Mice.Biomolecules · 2023Article
- Enhancement of nutraceutical and anti-diabetic potential of fenugreek (Trigonella foenum-graecum). Sprouts with natural elicitors.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Heart Uptake of [Pharmaceuticals (Basel, Switzerland) · 2022Article
- Blocking MG53Circulation research · 2022Article
- Isoform-Specific Role of GSK-3 in High Fat Diet Induced Obesity and Glucose Intolerance.Cells · 2022Article
- Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- Targeting Impaired Nutrient Sensing via the Glycogen Synthase Kinase-3 Pathway With Therapeutic Compounds to Prevent or Treat Dementia: A Systematic Review.Frontiers in aging · 2022Review
- Metabolism and Endocrine Disorders: What Wnt Wrong?Frontiers in endocrinology · 2022Review
- Mechanical Stretching-Induced Traumatic Brain Injury Is Mediated by the Formation of GSK-3β-Tau Complex to Impair Insulin Signaling Transduction.Biomedicines · 2021Article
- Placental Antioxidant Defenses and Autophagy-Related Genes in Maternal Obesity and Gestational Diabetes Mellitus.Nutrients · 2021Article
- Glucose Regulates Microtubule Disassembly and the Dose of Insulin Secretion via Tau Phosphorylation.Diabetes · 2020Article
- Mechanisms of the Regulation and Dysregulation of Glucagon Secretion.Oxidative medicine and cellular longevity · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
High glucose (HG) has been shown to induce insulin resistance in both type 1 and type 2 diabetes. However, the molecular mechanism behind this phenomenon is unknown. Insulin receptor substrate (IRS) proteins are the key signaling molecules that mediate insulin's intracellular actions. Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance. In this study we have shown that proteasome degradation of IRS1, but not of IRS2, is involved in HG-induced insulin resistance in Chinese hamster ovary (CHO) cells as well as in primary hepatocytes. To further investigate the molecular mechanism by which HG induces insulin resistance, we examined various molecular candidates with respect to their involvement in the reduction in IRS1 protein levels. In contrast to the insulin-induced degradation of IRS1, HG-induced degradation of IRS1 did not require IR signaling or phosphatidylinositol 3-kinase/Akt activity. We have identified glycogen synthase kinase 3beta (GSK3 beta or GSK3B as listed in the MGI Database) as a kinase required for HG-induced serine(332) phosphorylation, ubiquitination, and degradation of IRS1. Overexpression of IRS1 with mutation of serine(332) to alanine partially prevents HG-induced IRS1 degradation. Furthermore, overexpression of constitutively active GSK3 beta was sufficient to induce IRS1 degradation. Our data reveal the molecular mechanism of HG-induced insulin resistance, and support the notion that activation of GSK3 beta contributes to the induction of insulin resistance via phosphorylation of IRS1, triggering the ubiquitination and degradation of IRS1.
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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.