Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro

Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease
Sudeep P PushpakomMunir Pirmohamed

Abstract

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. 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. 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. Telm...Continue Reading

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Citations

Jan 14, 2021·American Journal of Physiology. Cell Physiology·Jérémy DufauDominique Langin
Aug 14, 2020·Virology·Praveen Kumar TripathiAshok Kumar Patel

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Methods Mentioned

BETA
enzyme-linked immunosorbent assays
ELISA
Assay

Software Mentioned

SPSS Statistics

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