Rat INS-1 cells treated with HIV-1 protease inhibitor Nelfinavir for 48 h showed that both basal and glucose-stimulated insulin secretion decreased, the latter was more marked, suggesting that long-term treatment with Nelfinavir may impair ?-cell function.

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

OBJECTIVETo investigate the effects of various HIV protease inhibitors on the function of pancreatic beta-cells.

METHODSRat insulinoma INS-1 cells were incubated with different concentrations of ritonavir or amprenavir for 48 h and stimulated with 20 mmol/L D-glucose for 30 min. The rate of insulin release was measured in the supernatant by ELISA, normalized to cellular DNA contents. Cells were counted with trypan blue and MTT test were determined to evaluate the effect of protease inhibitors on cell viability.

RESULTRitonavir treatment significantly decreased baseline insulin release and glucose-stimulated insulin release in a dose-dependent manner (r=-0.861, -0.839, both P<0.01). For 10 micromol/L of ritonavir, the decrease rate of baseline insulin secretion and glucose-stimulated insulin secretion was 46% and 47%, respectively. Amprenavir had no effect on the rate of insulin release.

CONCLUSIONVarious HIV protease inhibitors present different effect on the insulin release of pancreatic beta-cells.

Animals ; Carbamates ; pharmacology ; HIV Protease Inhibitors ; pharmacology ; Insulin ; secretion ; Insulinoma ; metabolism ; pathology ; Islets of Langerhans ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; Rats ; Ritonavir ; pharmacology ; Sulfonamides ; pharmacology