ArticleDiabetologia2004
Nelfinavir-induced insulin resistance is associated with impaired plasma membrane recruitment of the PI 3-kinase effectors Akt/PKB and PKC-zeta.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 50 citations in OpenAlex.
- Magnesium increases insulin-dependent glucose uptake in adipocytes.Frontiers in endocrinology · 2022Article
- Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors.International journal of molecular sciences · 2021Article
- The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process.International journal of molecular sciences · 2020Review
- The Anti-Angiogenic Effects of Anti-Human Immunodeficiency Virus Drugs.Frontiers in oncology · 2020Review
- Adipose Tissue in HIV Infection.Comprehensive Physiology · 2017Review
- Review
- Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line.Scientific reports · 2016Article
- Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B expression.Experimental and therapeutic medicine · 2014Article
- Nelfinavir suppresses insulin signaling and nitric oxide production by human aortic endothelial cells: protective effects of thiazolidinediones.Ochsner journal · 2013Article
- Molecular mechanisms for insulin resistance in treated HIV-infection.Best practice & research. Clinical endocrinology & metabolism · 2011Review
- GS-8374, a novel HIV protease inhibitor, does not alter glucose homeostasis in cultured adipocytes or in a healthy-rodent model system.Antimicrobial agents and chemotherapy · 2011Article
- Effects of HIV protease inhibitors on progression of monocrotaline- and hypoxia-induced pulmonary hypertension in rats.Circulation · 2010Article
- Postreceptoral adipocyte insulin resistance induced by nelfinavir is caused by insensitivity of PKB/Akt to phosphatidylinositol-3,4,5-trisphosphate.Endocrinology · 2009Article
- Antiretroviral-related adipocyte dysfunction and lipodystrophy in HIV-infected patients: Alteration of the PPARγ-dependent pathways.PPAR research · 2009Article
- HIV protease inhibitors and insulin resistance: lessons from in-vitro, rodent and healthy human volunteer models.Current opinion in HIV and AIDS · 2008Article
- Repositioning HIV protease inhibitors as cancer therapeutics.Current opinion in HIV and AIDS · 2008Article
- Article
- Article
- NFV, an HIV-1 protease inhibitor, induces growth arrest, reduced Akt signalling, apoptosis and docetaxel sensitisation in NSCLC cell lines.British journal of cancer · 2006Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisChronic exposure of 3T3-L1 adipocytes to the HIV protease inhibitor nelfinavir induces insulin resistance, recapitulating key metabolic alterations of adipose tissue in the lipodystrophy syndrome induced by these agents. Our goal was to identify the defect in the insulin signal transduction cascade leading to nelfinavir-induced insulin resistance.
methodsFully differentiated 3T3-L1 adipocytes were exposed to 30 micro mol/l nelfinavir for 18 h, after which the amount, the phosphorylation and the localisation of key proteins in the insulin signalling cascade were evaluated.
resultsInsulin-induced interaction of phosphatidylinositol 3'-kinase (PI 3-kinase) with IRS proteins was normal in cells treated with nelfinavir, as was IRS-1-associated PI 3-kinase activity. Yet insulin-induced phosphorylation of Akt/protein kinase B (PKB), p70S6 kinase and extracellular signal-regulated kinase 1/2 was significantly impaired. This could not be attributed to increased protein phosphatase 2A activity or to increased expression of phosphoinositide phosphatases (SHIP2 or PTEN). However, insulin failed to induce translocation of the PI 3-kinase effectors Akt/PKB and protein kinase C-zeta (PKC-zeta) to plasma membrane fractions of nelfinavir-treated adipocytes. CONCLUSIONS/
interpretationWe therefore conclude that nelfinavir induces a defect in the insulin signalling cascade downstream of the activation of PI 3-kinase. This defect manifests itself by impaired insulin-mediated recruitment of Akt/PKB and PKC-zeta to the plasma membrane.
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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 Socratic graph.