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Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro.
Diab Vasc Dis Res. 2018 05; 15(3):233-242.DV

Abstract

BACKGROUND

Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose-response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects.

METHODS

Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively. Adipokine secretion and expression of insulin signalling mediators were evaluated using enzyme-linked immunosorbent assays.

RESULTS

Telmisartan partially reversed the deleterious effects of antiretrovirals on adipocyte lipid accumulation, expression of adipogenic regulators (peroxisome proliferator receptor-gamma and lipin 1), adipokine secretion and expression of the insulin signalling mediator pAktSer473. The metabolic effects of telmisartan followed a non-monotonic response with the maximal effect observed at 5 µM in the primary human adipocyte model.

CONCLUSION

Telmisartan has beneficial metabolic effects in adipocytes in vitro, but its potential to reduce antiretroviral-induced cardiometabolic disease in HIV-infected individuals needs to be evaluated in a well-designed adequately powered clinical trial.

Authors+Show Affiliations

1 Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, UK.2 Warwick Medical School, University of Warwick, Coventry, UK.1 Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, UK.1 Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, UK.3 Department of Biomedical Sciences, University of Westminster, London, UK.2 Warwick Medical School, University of Warwick, Coventry, UK.2 Warwick Medical School, University of Warwick, Coventry, UK.1 Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29466880

Citation

Pushpakom, Sudeep P., et al. "Telmisartan Reverses Antiretroviral-induced Adipocyte Toxicity and Insulin Resistance in Vitro." Diabetes & Vascular Disease Research, vol. 15, no. 3, 2018, pp. 233-242.
Pushpakom SP, Adaikalakoteswari A, Owen A, et al. Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diab Vasc Dis Res. 2018;15(3):233-242.
Pushpakom, S. P., Adaikalakoteswari, A., Owen, A., Back, D. J., Tripathi, G., Kumar, S., McTernan, P., & Pirmohamed, M. (2018). Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diabetes & Vascular Disease Research, 15(3), 233-242. https://doi.org/10.1177/1479164118757924
Pushpakom SP, et al. Telmisartan Reverses Antiretroviral-induced Adipocyte Toxicity and Insulin Resistance in Vitro. Diab Vasc Dis Res. 2018;15(3):233-242. PubMed PMID: 29466880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. AU - Pushpakom,Sudeep P, AU - Adaikalakoteswari,Antonysunil, AU - Owen,Andrew, AU - Back,David J, AU - Tripathi,Gyanendra, AU - Kumar,Sudhesh, AU - McTernan,Philip, AU - Pirmohamed,Munir, Y1 - 2018/02/21/ PY - 2018/2/23/pubmed PY - 2018/10/3/medline PY - 2018/2/23/entrez KW - HIV KW - adipocyte KW - antiretroviral KW - insulin resistance KW - metabolic disease KW - telmisartan SP - 233 EP - 242 JF - Diabetes & vascular disease research JO - Diab Vasc Dis Res VL - 15 IS - 3 N2 - BACKGROUND: Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose-response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects. METHODS: Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively. Adipokine secretion and expression of insulin signalling mediators were evaluated using enzyme-linked immunosorbent assays. RESULTS: Telmisartan partially reversed the deleterious effects of antiretrovirals on adipocyte lipid accumulation, expression of adipogenic regulators (peroxisome proliferator receptor-gamma and lipin 1), adipokine secretion and expression of the insulin signalling mediator pAktSer473. The metabolic effects of telmisartan followed a non-monotonic response with the maximal effect observed at 5 µM in the primary human adipocyte model. CONCLUSION: Telmisartan has beneficial metabolic effects in adipocytes in vitro, but its potential to reduce antiretroviral-induced cardiometabolic disease in HIV-infected individuals needs to be evaluated in a well-designed adequately powered clinical trial. SN - 1752-8984 UR - https://www.unboundmedicine.com/medline/citation/29466880/Telmisartan_reverses_antiretroviral_induced_adipocyte_toxicity_and_insulin_resistance_in_vitro_ L2 - http://journals.sagepub.com/doi/full/10.1177/1479164118757924?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -