Abstract 425: Hydrogen Peroxide and 13-hydroperoxylinoleic Acid Induce the Expression of Insulin-like Growth Factor-binding Protein 3 in HepG2 Cells

Background Patients with type 2 diabetes are reported to have increased oxidative stress. Oxidized LDL is reported to suppress the expression of insulin-like growth factor I receptor (IGF1R). IGF1 emerges as a potential therapeutic target for insulin resistance and deficiency. The functions of IGF1 are regulated by its receptors as well as binding proteins (IGFBPs). IGFBP3 is known as the main binding protein for IGF1, and shows inhibitory effects on IGF1 through binding to extracellular matrix. The present study investigates whether oxidative stress regulates IGF binding proteins. Methods HepG2 (hepatocellular carcinoma) cells were treated with either hydrogen peroxide (H2O2) or 13-hydroperoxylinoleic acid (HPODE) with/without catalase in serum free medium for 24 hours, and total RNA and protein were isolated for quantitative PCR or Western blot analyses. Results H2O2 of variant concentrations induced IGFBP3 expression, which was abolished by the addition of catalase. HPODE also induced IGFBP3 expression in a dose-dependent manner. The induction was found for both isoforms A and B of IGFBP3. Conclusion Our findings shed light on the potential synergetic regulation of IGF1 by oxidative stress through both the receptor and binding protein, and advance the understanding of the IGF1 resistance in type 2 diabetes. Furthermore, antioxidants are indicated to be able to increase the IGF1 sensitivity, and reduce the dosage and side effects of IGF1 administration for patients with diabetes.