HIV protease inhibitors induce metabolic dysfunction in part via increased JNK1/2 pro-inflammatory signaling in L6 cells

• Published in: Antiviral research 2011-12, Vol.92 (3), p.415-423
• Main Authors: Bogachus, Lindsey D., Turcotte, Lorraine P.
• Format: Article
• Language: English
• Subjects: AKT2; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Atazanavir Sulfate; Biological and medical sciences; Cell Line; Fatty acid oxidation; Glucose - metabolism; Glucose uptake; HIV Protease Inhibitors - pharmacology; Human immunodeficiency virus; Inflammation; Insulin Resistance; Medical sciences; Mitogen-Activated Protein Kinase 8 - metabolism; Mitogen-Activated Protein Kinase 9 - metabolism; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - enzymology; Muscle Fibers, Skeletal - metabolism; Oligopeptides - pharmacology; Oxidation-Reduction - drug effects; p38 MAPK (Mitogen Activated Protein Kinase); p38 Mitogen-Activated Protein Kinases - metabolism; Palmitates - metabolism; Pharmacology. Drug treatments; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Pyridines - pharmacology; Rats; Ritonavir - pharmacology; Signal Transduction - drug effects; Time Factors
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2011.09.008

► Atazanavir sulfate+ritonavir treatment increases glucose and fatty acid metabolism. ► Atazanavir sulfate+ritonavir treatment induces a pro-inflammatory state. ► The protease inhibitor-induced pro-inflammatory state induces insulin resistance. Protease inhibitors (PIs), such as atazanavir sulfate and ritonavir, are used clinically to prevent the progression of HIV and are known to induce insulin resistance. To determine whether PI-mediated insulin resistance is induced by activation of pro-inflammatory cascades, L6 skeletal muscle cells were treated ±atazanavir sulfate, ritonavir, or atazanavir sulfate+ritonavir, and ±insulin. Treatment with atazanavir sulfate, ritonavir, or atazanavir sulfate+ritonavir for 24 or 48h significantly increased basal glucose uptake (P