The IGF/IGF-IR-independent actions of IGFBP-3 have been shown to contribute to the pathophysiology of various human diseases such as cancer, diabetes, obesity, fatty liver disease, ischemia, and Alzheimer’s disease [15,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47]. This evidence concerns the gene IGFBP3 and ischemia.