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.
journal_name
Diab Vasc Dis Resjournal_title
Diabetes & vascular disease researchauthors
Pushpakom SP,Adaikalakoteswari A,Owen A,Back DJ,Tripathi G,Kumar S,McTernan P,Pirmohamed Mdoi
10.1177/1479164118757924subject
Has Abstractpub_date
2018-05-01 00:00:00pages
233-242issue
3eissn
1479-1641issn
1752-8984journal_volume
15pub_type
杂志文章abstract::Cardiovascular disease is the most common complication of type 2 diabetes mellitus (type 2 DM), accounting for approximately 80% of deaths. While atherosclerotic vascular disease accounts for much of the cardiovascular morbidity and mortality among diabetic patients, congestive heart failure (CHF) is another key compl...
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