title: Molecular mechanisms for insulin resistance in treated HIV-infection.
abstract: Identification and characterization of the molecular mechanisms contributing to the high incidence of insulin resistance in HIV infected patients treated with combined antiretroviral therapy remains a critically important goal in the quest to improve the safety of antiretroviral treatment regimens. The use of in vitro model systems together with the investigation of drug-mediated effects on glucose homeostasis in animals and healthy human volunteers has provided important insight into the contribution of individual drugs to insulin resistance and affected cellular pathways. HIV protease inhibitor mediated blockade of glucose transport and nucleoside reverse transcriptase inhibitor mediated mitochondrial toxicity have been well characterized. Together with growing understanding of mediators of insulin resistance in non-HIV metabolic syndrome, additional cellular effects including the induction of endoplasmic reticulum and oxidative stress, altered adipocytokine secretion, and lipotoxicity have been integrated into this developing picture. Further elucidation of these mechanisms provides potential for the continued development of safer antiviral drugs and targeted treatment of insulin resistance in affected patients.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA. hruz_p@kids.wustl.edu
authors.forename: Paul W
authors.initials: PW
authors.lastname: Hruz
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors