Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors

A. Rudich, R. Ben-Romano, S. Etzion, N. Bashan

Research output: Contribution to journalReview articlepeer-review

55 Scopus citations


Accumulating clinical evidence now links HIV protease inhibitors (HPIs) to the pathogenesis of insulin resistance, dyslipidaemia, lipodystrophy and atherosclerosis associated with highly active anti-retroviral therapy. Here we briefly describe the evidence for a distinct causative role for HPIs, and explore the cellular mechanisms proposed to underlie these side-effects. Acute inhibition of GLUT4-mediated glucose transport, and defective insulin signalling induced by chronic exposure to nelfinavir, are described as cellular mechanisms of insulin resistance. Interference with adipogenesis and adipocyte apoptosis and nelfinavir-induced activation of lipolysis are discussed as potential mechanisms of HPI-induced lipodystrophy. HPI-induced free radical production, apoptosis and increased glucose utilization in vascular smooth muscle cells are presented as possible novel mechanisms for atherosclerosis. Common pathways and cause-effect relationships between the various cellular mechanisms presented are then discussed, with emphasis on the role of insulin resistance, free radical production and enhanced lipolysis. Understanding the cellular mechanisms of HPI-induced side-effects will enhance the search for improved anti-retroviral therapy, and may also shed light on the pathogenesis of common forms of insulin resistance, dyslipidaemia and atherosclerosis.

Original languageEnglish
Pages (from-to)75-88
Number of pages14
JournalActa Physiologica Scandinavica
Issue number1
StatePublished - 1 Jan 2005


  • Adipocytes
  • Apoptosis
  • Dyslipidaemia
  • Free fatty acids
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology


Dive into the research topics of 'Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors'. Together they form a unique fingerprint.

Cite this