ArticlePloS one2011
HIV protease inhibitors act as competitive inhibitors of the cytoplasmic glucose binding site of GLUTs with differing affinities for GLUT1 and GLUT4.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Characterization and risk stratification of coronary artery disease in people living with HIV: a global systematic review.Frontiers in cardiovascular medicine · 2025Pooled it
- Improved adipose tissue function with initiation of protease inhibitor-only ART.The Journal of antimicrobial chemotherapy · 2016Trial
- Targeting GLUTs in Cancer: Mechanisms, Combination Strategies, and Translational Challenges.Current medical science · 2026Review
- A distinct form of fat fibrosis is linked to insulin resistance in people with HIV.JCI insight · 2026Observational
- The state of the art in secondary pharmacology and its impact on the safety of new medicines.Nature reviews. Drug discovery · 2024Review
- HIV-Associated Hypertension: Risks, Mechanisms, and Knowledge Gaps.Circulation research · 2024Review
- Article
- An Open-Label Phase I Study of Metformin and Nelfinavir in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.Clinical lymphoma, myeloma & leukemia · 2024Article
- D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.PNAS nexus · 2024Article
- Adipose Tissue Dysfunction and Energy Balance Paradigms in People Living With HIV.Endocrine reviews · 2024Review
- Harnessing Immune Cell Metabolism to Modulate Alloresponse in Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Study on Saccharide-Glucose Receptor Interactions with the Use of Surface Plasmon Resonance.International journal of molecular sciences · 2023Article
- Small molecule inhibitors for cancer metabolism: promising prospects to be explored.Journal of cancer research and clinical oncology · 2023Review
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Autocrine FGF1 signaling promotes glucose uptake in adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- An overview of the Plasmodium falciparum hexose transporter and its therapeutic interventions.Proteins · 2022Review
- Metabolic Complications of Chronic HIV Infection: A Narrative Review.Pathogens (Basel, Switzerland) · 2022Review
- Drug Discovery of Plausible Lead Natural Compounds That Target the Insulin Signaling Pathway: Bioinformatics Approaches.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- A Step Closer to the "Fourth 90": A Practical Narrative Review of Diagnosis and Management of Nutritional Issues of People Living with HIV.Diagnostics (Basel, Switzerland) · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The clinical use of several first generation HIV protease inhibitors (PIs) is associated with the development of insulin resistance. Indinavir has been shown to act as a potent reversible noncompetitive inhibitor of zero-trans glucose influx via direct interaction with the insulin responsive facilitative glucose transporter GLUT4. Newer drugs within this class have differing effects on insulin sensitivity in treated patients. GLUTs are known to contain two distinct glucose-binding sites that are located on opposite sides of the lipid bilayer. To determine whether interference with the cytoplasmic glucose binding site is responsible for differential effects of PIs on glucose transport, intact intracellular membrane vesicles containing GLUT1 and GLUT4, which have an inverted transporter orientation relative to the plasma membrane, were isolated from 3T3-L1 adipocytes. The binding of biotinylated ATB-BMPA, a membrane impermeable bis-mannose containing photolabel, was determined in the presence of indinavir, ritonavir, atazanavir, tipranavir, and cytochalasin b. Zero-trans 2-deoxyglucose transport was measured in both 3T3-L1 fibroblasts and primary rat adipocytes acutely exposed to these compounds. PI inhibition of glucose transport correlated strongly with the PI inhibition of ATB-BMPA/transporter binding. At therapeutically relevant concentrations, ritonavir was not selective for GLUT4 over GLUT1. Indinavir was found to act as a competitive inhibitor of the cytoplasmic glucose binding site of GLUT4 with a K(I) of 8.2 µM. These data establish biotinylated ATB-BMPA as an effective probe to quantify accessibility of the endofacial glucose-binding site in GLUTs and reveal that the ability of PIs to block this site differs among drugs within this class. This provides mechanistic insight into the basis for the clinical variation in drug-related metabolic toxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.