title: Insulin inhibits lipopolysaccharide-induced nitric oxide synthase expression in rat primary astrocytes.
abstract: Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) from reactive astrocytes and microglia may contribute to the development of many types of neurological diseases. Insulin has been shown to inhibit the expression of iNOS, in several organs and cell types. Although insulin and its receptors are present in the central nervous system, the effects of insulin on the iNOS pathway in the brain have not been determined. In this study, using lipopolysaccharide (LPS)-stimulated astrocytes as a model of reactive astrocytes, we investigated the effects of insulin on iNOS expression in activated astrocytes and the mechanism involved. The expression of iNOS was significantly upregulated by LPS in astrocytes. Insulin applied prior to LPS, dose-dependently inhibited LPS-induced iNOS gene expression and iNOS protein levels. In agreement with the suppressive effects of insulin on iNOS expression, insulin also inhibited LPS-induced iNOS activity and NO production. Moreover, insulin was found to significantly inhibit LPS-induced IκB-α phosphorylation and degradation, which led to a decrease in levels of the p65 subunit of NF-κB in the nuclear fraction. Therefore, insulin inhibited LPS-induced iNOS expression via suppressing NF-κB pathway in astrocytes. In addition, treatment with insulin had no effect on LPS-induced PKB phosphorylation. Based on our results, it is plausible to speculate that insulin in the brain may play a neuroprotective role in neurological disorders by controlling the release of NO via the regulation of iNOS expression in astrocytes.
authors: Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, PR China.
authors: Hui
authors: H
authors: Li
authors: Baoyi
authors: B
authors: Liu
authors: Jingyang
authors: J
authors: Huang
authors: Haili
authors: H
authors: Chen
authors: Xiaosun
authors: X
authors: Guo
authors: Zhongrui
authors: Z
authors: Yuan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II