Title : Nelfinavir-induced insulin resistance is associated with impaired plasma membrane recruitment of the PI 3-kinase effectors Akt/PKB and PKC-zeta.

Pub. Date : 2004 Jun

PMID : 15168016






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1 Nelfinavir-induced insulin resistance is associated with impaired plasma membrane recruitment of the PI 3-kinase effectors Akt/PKB and PKC-zeta. Nelfinavir insulin Homo sapiens
2 AIMS/HYPOTHESIS: Chronic exposure of 3T3-L1 adipocytes to the HIV protease inhibitor nelfinavir induces insulin resistance, recapitulating key metabolic alterations of adipose tissue in the lipodystrophy syndrome induced by these agents. Nelfinavir insulin Homo sapiens
3 Our goal was to identify the defect in the insulin signal transduction cascade leading to nelfinavir-induced insulin resistance. Nelfinavir insulin Homo sapiens
4 Our goal was to identify the defect in the insulin signal transduction cascade leading to nelfinavir-induced insulin resistance. Nelfinavir insulin Homo sapiens
5 METHODS: Fully differentiated 3T3-L1 adipocytes were exposed to 30 micro mol/l nelfinavir for 18 h, after which the amount, the phosphorylation and the localisation of key proteins in the insulin signalling cascade were evaluated. Nelfinavir insulin Homo sapiens
6 RESULTS: Insulin-induced interaction of phosphatidylinositol 3"-kinase (PI 3-kinase) with IRS proteins was normal in cells treated with nelfinavir, as was IRS-1-associated PI 3-kinase activity. Nelfinavir insulin Homo sapiens
7 CONCLUSIONS/INTERPRETATION: We therefore conclude that nelfinavir induces a defect in the insulin signalling cascade downstream of the activation of PI 3-kinase. Nelfinavir insulin Homo sapiens