INS and Alzheimer disease: Therefore, another impact of RAS in the aspect of AD might be impaired insulin signaling and its contribution to IR (Folli et al., 1999) through mechanisms mentioned in Sections “Neurons” and “Oxidative Stress.” Interestingly, a significant increase in intracellular ACE was shown in high glucose conditions despite no change in extracellular ACE under the same circumstances (Cristovam et al., 2008).