Effects of various HIV protease inhibitors on function of rat insulinoma cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of various HIV protease inhibitors on the function of pancreatic beta-cells.</p><p><b>METHODS</b>Rat 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.</p><p><b>RESULT</b>Ritonavir 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.</p><p><b>CONCLUSION</b>Various HIV protease inhibitors present different effect on the insulin release of pancreatic beta-cells.</p>

Impairment of IRS-2 signaling in rat insulinoma INS-1 cells by nelfinavir / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate whether HIV-1 protease inhibitor nelfinavir alters the insulin stimulated phosphorylation of insulin signaling parameters in rat insulinoma INS-1 cells.</p><p><b>METHODS</b>INS-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.</p><p><b>RESULT</b>Nelfinavir 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.</p><p><b>CONCLUSION</b>Treatment with nelfinavir might impair IRS-2-mediated signaling in pancreatic beta cells.</p>