NOS1 and Hyperglycemia: Research indicated that sustained hyperglycemia can cause an increase of glutamate, N-methyl-D-aspartate receptor (NMDA) receptor dysfunction, and Ca2+/CaM-dependent nNOS activity increase, and the overproduction of NO would result in the enhancement of LTP (Yang et al., 1999; Biessels et al., 2002a).