Ismail, Wan IryaniKing, Judy A.Anwar, KhawarPillay, Tahir S.2014-06-062014-06-062013Ismail, WIW, King, JA, Anwar, K & Pillay, TS 2013, 'Indinavir and nelfinavir inhibit proximal insulin receptor signaling and salicylate abrogates inhibition : potential role of the NFkappa B pathway', Journal of cellular biochemistry, vol. 114, no. 8, pp. 1729-1737.0730-2312 (print)1097-4644 (online)10.1002/jcb.24513http://hdl.handle.net/2263/40054The molecular basis of insulin resistance induced by HIV protease inhibitors (HPIs) remains unclear. In this study, Chinese hamster ovary cells transfected with high levels of human insulin receptor (CHO-IR) and 3T3-L1 adipocytes were used to elucidate the mechanism of this side effect. Indinavir and nelfinavir induced a significant decrease in tyrosine phosphorylation of the insulin receptor b-subunit. Indinavir caused a significant increase in the phosphorylation of insulin receptor substrate-1 (IRS-1) on serine 307 (S307) in both CHO-IR cells and 3T3-L1 adipocytes. Nelfinavir also inhibited phosphorylation of Map/ERK kinase without affecting insulin-stimulated Akt phosphorylation. Concomitantly, levels of protein tyrosine phosphatase 1B (PTP1B), suppressor of cytokines signaling-1 and -3 (SOCS-1 and -3), Src homology 2B (SH2B) and adapter protein with a pleckstrin homology domain and an SH2 domain (APS) were not altered significantly. When CHO-IR cells were pre-treated with sodium salicylate (NaSal), the effects of indinavir on tyrosine phosphorylation of the IR b-subunit and phosphorylation of IRS-1 at S307 were abrogated. These data suggest a potential role for the NFkB pathway in insulin resistance induced by HPIs.en© 2013 Wiley Periodicals, Inc. The definite version is available at : http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-4644Insulin resistanceSalicylateHIV protease inhibitors (HPIs)Preprint Article