Saquinavir induces insulin resistance in rat INS-1 cells / 中国糖尿病杂志

ABSTRACT

Objective To investigate the effect of HIV-1 protease inhibitor saquinavir on insulin signaling and β-cell function in rat INS-1 cells. Methods INS-1 cells were preincubated with 0 or 10 μmol/L saquinavir for 48 h, stimulated with 100 nmol/L insulin for 2 min or 20 mmol/L glucose for 30 min. Insulin signaling parameters were analyzed by immunoprecipitation and Western blot on cell lysates. Insulin concentrations in the supernatant were measured by ELISA, and standardized by cellular DNA contents. Cell count with trypan blue stain and MTT test were determined to evaluate the effect of saquinavir on cell viability. Results Treatment with saquinavir for 48 h significantly decreased insulin-stimulated phosphorylation of IRS-1, IRS-2 and Thr~(308)-phosphorylation of Akt in INS-1 cells by 60%, 66% and 55%, decreased the rate of basal insulin secretion and glucose-stimulated insulin release by 39% and 49% compared with control cells, respectively. Conclusions Treatment with saquinavir impairs insulin signal transmission in pancreatic β cells and results in insulin resistance in β cells. This effect might influence the function of β cells.