Conflicts of interest: nothing to declare.
Indinavir and nelfinavir inhibit proximal insulin receptor signaling and salicylate abrogates inhibition: Potential role of the NFkappa B pathway†
Article first published online: 11 JUN 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 8, pages 1729–1737, August 2013
How to Cite
Ismail, W. I. W., King, J. A., Anwar, K. and Pillay, T. S. (2013), Indinavir and nelfinavir inhibit proximal insulin receptor signaling and salicylate abrogates inhibition: Potential role of the NFkappa B pathway. J. Cell. Biochem., 114: 1729–1737. doi: 10.1002/jcb.24513
- Issue published online: 11 JUN 2013
- Article first published online: 11 JUN 2013
- Accepted manuscript online: 5 FEB 2013 08:17AM EST
- Manuscript Accepted: 24 JAN 2013
- Manuscript Received: 4 OCT 2012
- National Research Foundation (Rated Researcher Incentive funding) of South Africa
- National Health Laboratory Service, South Africa
- Young Lecturer Scheme under Universiti Teknologi MARA
- Ministry of Higher Education of Malaysia
- HIV PROTEASE INHIBITORS;
- INSULIN RESISTANCE;
The 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 β-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 β-subunit and phosphorylation of IRS-1 at S307 were abrogated. These data suggest a potential role for the NFκB pathway in insulin resistance induced by HPIs. J. Cell. Biochem. 114: 1729–1737, 2013. © 2013 Wiley Periodicals, Inc.