OBJECTIVETo investigate whether HIV-1 protease inhibitor nelfinavir alters the insulin stimulated phosphorylation of insulin signaling parameters in rat insulinoma INS-1 cells.

METHODSINS-1 cells were incubated with nelfinavir for 48 h and stimulated with 100 nmol/L insulin for 2 min. Immunoprecipitation and Western blot analysis of the insulin stimulated insulin receptor substrate (IRS)-1,-2 and Akt-Thr(308) phosphorylation were performed on cell lysates. Cytotoxic effects of nelfinavir were measured by cell count with trypan blue and MTT reduction test.

RESULTNelfinavir decreased insulin stimulated phosphorylation of IRS-2 and Akt-Thr(308) in a dose-dependent manner; for 10 micromol/L of nelfinavir, the decrease was 52% and 55%, respectively.

CONCLUSIONTreatment with nelfinavir might impair IRS-2-mediated signaling in pancreatic beta cells.

Animals ; Cell Line, Tumor ; Cell Survival ; drug effects ; HIV Protease Inhibitors ; pharmacology ; Insulin Receptor Substrate Proteins ; Insulinoma ; metabolism ; Intracellular Signaling Peptides and Proteins ; Islets of Langerhans ; drug effects ; physiology ; Nelfinavir ; pharmacology ; Pancreatic Neoplasms ; metabolism ; Phosphoproteins ; analysis ; physiology ; Protein-Serine-Threonine Kinases ; analysis ; Proto-Oncogene Proteins ; analysis ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction ; drug effects