Level of the brain IGF-I protein expression in the insulin resistant animal model

In insulin resistance animal models, insulin uptake from periphery to the brain is impaired. While insulin is not involved in glucose transfer to the neurons, it is required for neuron survival and function through binding to its receptor. Furthermore, an insulin homologue called insulin like growth factor [IGF-I] is abundantly expressed in mature rats, acts in parallel with the insulin in brain, binds to the insulin receptor and its serum levels reduced in insulin resistance. In this study, we sought to investigate whether the expression of brain IGF-I is altered in the insulin resistant animal model. Wistar rats were fed with 10% fructose in their drinking water up to 4 months and induced with the insulin resistance. The rats were killed, perfused with 4% PFA, and their brains were sectioned and studied for the immunoreactivity of the IGF-I. Results showed that there is an increased intensity of IGF-I in most brain areas. Altogether, despite the low levels or lack of insulin in brain of the insulin resistant animal model, increased expression of the brain suggests a compensatory mechanism to maintain the insulin function

[Investigation on the levels of IGF-I receptor and IGF-I binding protein I in the brain of insulin resistant rats]

There is limited knowledge available on the metabolism of glucose in the brain, an insulin insensitive organ. Insulin receptors hybridize with insulin like growth factor receptor [IGF-I] to transducer the signals in different areas of the brain. In this article we aimed at investigating whether the expression of IGF-I receptor and IGF-I binding proteins [IGFBP1] is changed in the brain of the diabetic animal model. To induce insulin resistance, adult wistar rats were fed with fructose in their drinking water [10%]. The expression of IGF-I receptor and its binding protein were examined immunohistochemically. Our findings demonstrated that the expression of IGF-I receptor and IGF-I binding protein were not changed in different areas of the brain in insulin resistant rats, compared to those in the control rats. The unchanged expression levels of IGF-I and its binding protein I not imply the lack of involvement of the IGF-I signal transduction pathway in the insulin resistant brain, further investigations are to clarify the issue

Antisense RNA to the type I insulin-like growth factor receptor reversed the transformed phenotype of PC-3 human prostate cancer cell line in vitro

The insulin-like growth factor I receptor [IGF-IR] plays an essential role in the establishment and maintenance of transformed phenotype. Interference with the IGF- IR pathway by antisense causes reversal of the transformed phenotype in many rodent and human tumor cell lines. We stably transfected the PC-3 human prostate cancer cell line with an IGF-IR antisense RNA expression plasmid. The number of lGF-I receptors on the antisense-transfected PC-3 cells was reduced by 40.2% relative to the control-transfected cells. The transfected cells maintained their high expression of IGF-IR antisense RNA for up to one year in selective medium. The reduction in the expression of IGF-IR had no effect on the cell growth in monolayer. The clonogenicity of antisense-transfected cells was 24.7% of the clonogenicity of control-transfected cells in soft agar. There was a good correlation between IGF-IR level and inhibition of transformation in soft agar. These results indicate that reduction of IGF-IR by antisense RNA can reverse the transformed phenotype of human prostate cancer cells