Print Email Facebook Twitter Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B Title Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B Author Heemskerk, M.M. van den Berg, S.A. Pronk, A.C.M. van Klinken, J.B. Boon, M.R. Havekes, L.M. Rensen, P.C.N. Willems van Dijk, K. van Harmelen, V. Publication year 2014 Abstract The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the underlying mechanisms are poorly understood. The current study addressed the effects of long-term niacin treatment on insulin-mediated inhibition of adipocyte lipolysis and focused on the regulation of cAMP levels. APOE*3-Leiden.CETP transgenic mice treated with niacin for 15 wk were subjected to an insulin tolerance test and showed whole body insulin resistance. Similarly, adipocytes isolated from niacin-treated mice were insulin resistant and, interestingly, exhibited an increased response to cAMP stimulation by 8Br-cAMP, β1- and β2-adrenergic stimulation. Gene expression analysis of the insulin and β-adrenergic pathways in adipose tissue indicated that all genes were downregulated, including the gene encoding the cAMP-degrading enzyme phosphodiesterase 3B (PDE3B). In line with this, we showed that insulin induced a lower PDE3B response in adipocytes isolated from niacin-treated mice. Inhibiting PDE3B with cilostazol increased lipolytic responsiveness to cAMP stimulation in adipocytes. These data show that long-term niacin treatment leads to a downregulation of PDE3B in adipocytes, which could explain part of the observed insulin resistance and the increased responsiveness to cAMP stimulation. © 2014 the American Physiological Society. Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingAdenosine 3'-,5'-cyclic monophosphateAdipose tissueLipolysisPhosphodiesterases To reference this document use: http://resolver.tudelft.nl/uuid:b93f1b39-79e6-42d8-9d97-4067785ad047 DOI https://doi.org/10.1152/ajpendo.00641.2013 TNO identifier 503256 ISSN 1522-1555 Source American Journal of Physiology - Endocrinology and Metabolism, 306 (7), E808-E813 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.