Effects Of IGFs On Beta-Cell Proliferation In Ovine Models Exposed To Intrauterine Growth Restriction
AuthorOgunbunmi, Elizabeth Titlayo
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PublisherThe University of Arizona.
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AbstractAn intrauterine growth restricted fetus refers to a fetus that has failed to reach its genetic growth potential due to maternal or placental limitations that lower the supply of oxygen and nutrients (Barry & Anthony, 2008). The fetus is sensitive to nutrient deficiencies and responds by altering organ growth and development, specifically nutrient sensing tissues like insulin producing, pancreatic beta cells. Insulin-like growth factor-1 (IGF-1) modulates beta-cell proliferation, and insulin-like growth factor binding proteins (IGFBPs) regulate IGFs via transport and distribution (Duan & Xu, 2005). Previous reports have shown that IGF-1 is lower and IGFBP-2 is higher in islets from IUGR fetal sheep (Chen, Rozance, Hay Jr., & Limesand, 2012). We hypothesize that decreases in IGF-1 signaling lower beta-cell proliferation rates. We propose two possible mechanisms: IGFBP2 is up-regulated to activate IGF-1 or IGFBP2 to prevents IGF-1 activity. In the present study, we investigated the interaction of IGF-1 and IGFBP-2 on the regulation of beta cell proliferation in pancreatic islets of IUGR and control fetuses. Isolated islets were cultured in media containing IGF-1, IGFBP-2, IGF-1 + IGFBP-2, and T3 and compared to media without supplemented hormones. Proliferation was measured by incubating the islets with 5-Ethynyl-2'-deoxyuridine (EdU). After 48 h in culture the islets were prepared for histology. Beta cells were immunostained with guinea pig anti-porcine insulin polyclonal antibody, Edu with the Click-It assay to measure proliferation, and nuclei with DAPI. Fluorescent images were taken with a digital camera. A thorough understanding of beta-cell physiology prenatally can possibly predict the onset of diabetes in adult patients.
Degree ProgramHonors College