Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro
| Autor: | Antonysunil Adaikalakoteswari, Sudhesh Kumar, Philip G. McTernan, David Back, Sudeep Pushpakom, Andrew Owen, Gyanendra Tripathi, Munir Pirmohamed |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism antiretroviral Peroxisome proliferator-activated receptor Adipokine Pharmacology telmisartan adipocyte Benzoates 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Insulin resistance Adipokines Adipocyte Diabetes mellitus insulin resistance Internal Medicine medicine Adipocytes Animals 030212 general & internal medicine Antihypertensive Agents chemistry.chemical_classification business.industry HIV Lipid metabolism Cell Differentiation Original Articles medicine.disease Lipid Metabolism metabolic disease PPAR gamma 030104 developmental biology chemistry Adipogenesis Benzimidazoles Telmisartan Cardiology and Cardiovascular Medicine business medicine.drug RC |
| Zdroj: | Diabetes & Vascular Disease Research Diabetes & vascular disease research |
| ISSN: | 1479-1641 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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