TY - JOUR TI - The actions of IGFBPs on growth and glucose metabolism in transgenic mouse models DO - https://doi.org/doi:10.7282/T3JS9Q5B PY - 2010 AB - The roles of insulin/IGF signaling in growth control and glucose metabolism have been extensively studied. To date, the growth inhibitory effects of IGFBPs and impaired glucose homeostasis caused by IGFBP-3 have been mostly studied in vitro. Our study, here, provides the first in vivo evidence by targeted gene deletion to show that IGFBP-2, -3, and -5 have inhibitory effects on growth, whereas IGFBP-4 and -6 have no effect. However, only male IGFBP-3 KO mice have increased body weight, indicating a gender difference in the system. IGFBP-4 mice, in either C57BL/6J or 129S6 background, show no difference from wild type animals. Disrupting the ternary complex of IGF/IGFBP by knocking out IGFBP-3 and -5 at the same time has a tremendous effect in growth of female mice. As a result, double KO mice gain even more weight than single IGFBP-3 or -5 KO mice. Disruption of the most abundant IGFBP-3 in circulation results in enhanced glucose tolerance companied by increased insulin secretion and insulin sensitivity. This makes IGFBP-3 a potential target in treating obesity and type 2 diabetes. Lastly, the effect of IGFBPs in traumatic brain injury was studied and it shows that, following brain injury, IGFBP-2 mRNA expression is upregulated at the injury site with the consequence that IGFBP-2 KO mice have significantly increased neurogenesis around the subventricular zone (SVZ). The role of IGFBP-2 in proliferation of stem cells in the CNS is further confirmed by quantitative PCR which shows a 28-fold upregulation in cultured neurospheres from the postnatal brain compared to Stratagene’s Universal Mouse Reference cDNA. KW - Neuroscience KW - Glucose--Metabolism KW - Insulin--Receptors KW - Repressors, Genetic KW - Mice--Growth KW - Mice as laboratory animals LA - eng ER -