[Impairment of IRS-2 signaling in rat insulinoma INS-1 cells by nelfinavir].
To investigate whether HIV-1 protease inhibitor nelfinavir alters the insulin stimulated phosphorylation of insulin signaling parameters in rat insulinoma INS-1 cells.



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.



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.



Treatment with nelfinavir might impair IRS-2-mediated signaling in pancreatic beta cells.
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. zhoujq@medmail.com.cn
Jia-qiang
JQ
Zhou
Zun
Z
Xiang
Morten
M
Schutt
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007340:Insulinoma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D019888:Nelfinavir / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D017320:HIV Protease Inhibitors; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019888:Nelfinavir