Impairment of IRS-2 signaling in rat insulinoma INS-1 cells by nelfinavir.
- Author:
Jia-qiang ZHOU
1
;
Zun XIANG
;
Morten SCHUTT
Author Information
- Publication Type:Journal Article
- MeSH: 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
- From: Journal of Zhejiang University. Medical sciences 2004;33(4):311-314
- CountryChina
- Language:Chinese
-
Abstract:
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.
