ReviewInternational journal of molecular sciences2022
Hexokinase-2-Linked Glycolytic Overload and Unscheduled Glycolysis-Driver of Insulin Resistance and Development of Vascular Complications of Diabetes.
Review in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 2026Review
- H19 inhibition orchestrates DNMT3B-dependent epigenetic reprogramming of glycolytic enzymes in the liver during diabetes.Cell communication and signaling : CCS · 2026Article
- The Burden of Preoperative Stress: Biological Mechanisms and Postoperative Outcomes.Brain sciences · 2026Review
- Mitochondrial oxidative stress under hypoxia promotes gastric mucosal injury in portal hypertensive gastropathy.Biomedical reports · 2026Article
- Insights Into the HIF-1α-Mediated NLRP3 Pyroptosis Pathway in the Regulation of Musculoskeletal Diseases in the High-Altitude Environment.Journal of inflammation research · 2026Review
- Dysregulation of the Glycolytic Entry Gate and Survival Route by Advanced Lipoxidation End Products in Diabetes Mellitus.Journal of ophthalmology · 2026Article
- Article
- Structural Characterization and In Vitro Hypoglycemic Activity of a Polysaccharides Obtained fromMolecules (Basel, Switzerland) · 2025Article
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- The triglyceride-glucose index: updating evidence from clinical settings to molecular mechanisms in ageing-related cerebrovascular diseases.Cardiovascular diabetology · 2025Review
- The Inflammatory Bridge Between Type 2 Diabetes and Neurodegeneration: A Molecular Perspective.International journal of molecular sciences · 2025Review
- Comprehensive Multi-Omics Analysis of Muscle Tissue Alterations in MaleInternational journal of molecular sciences · 2025Article
- Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mitochondria-Targeted Biomaterials-Regulating Macrophage Polarization Opens New Perspectives for Disease Treatment.International journal of nanomedicine · 2025Review
- The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products.International journal of medical sciences · 2025Review
- Circadian rhythm, glucose metabolism and diabetic complications: the role of glucokinase and the enlightenment on future treatment.Frontiers in physiology · 2025Review
- Methyltransferase-like 3 is a target for the diagnose and therapy of clear cell renal carcinoma.Frontiers in pharmacology · 2025Review
- The Role of Mitochondrial Regulation in Macrophage Polarization: Implications for the Pathogenesis of Rheumatoid Arthritis.Journal of inflammation research · 2025Review
- Advances in mitochondrial dysfunction in radiation tissue injury.Frontiers in physiology · 2025Review
- The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors.Cell communication and signaling : CCS · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The recent discovery of the glucose-induced stabilization of hexokinase-2 (HK2) to proteolysis in cell dysfunction in model hyperglycemia has revealed a likely key initiating factor contributing to the development of insulin resistance and vascular complications in diabetes. Consequently, the increased flux of glucose metabolism without a change in the expression and activity of glycolytic enzymes produces a wave of increased glycolytic intermediates driving mitochondrial dysfunction and increased reactive oxygen species (ROS) formation, the activation of hexosamine and protein kinase C pathways, the increased formation of methylglyoxal-producing dicarbonyl stress, and the activation of the unfolded protein response. This is called HK2-linked glycolytic overload and unscheduled glycolysis. The conditions required to sustain this are GLUT1 and/or GLUT3 glucose uptake and the expression of HK2. A metabolic biomarker of its occurrence is the abnormally increased deposition of glycogen, which is produced by metabolic channeling when HK2 becomes detached from mitochondria. These conditions and metabolic consequences are found in the vasculature, kidneys, retina, peripheral nerves, and early-stage embryo development in diabetes and likely sustain the development of diabetic vascular complications and embryopathy. In insulin resistance, HK2-linked unscheduled glycolysis may also be established in skeletal muscle and adipose tissue. This may explain the increased glucose disposal by skeletal uptake in the fasting phase in patients with type 2 diabetes mellitus, compared to healthy controls, and the presence of insulin resistance in patients with type 1 diabetes mellitus. Importantly, glyoxalase 1 inducer-
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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.