Figure 1.

Summary of plausible shared mechanisms for the pathogenetic association between schizophrenia and type 2 diabetes mellitus (T2DM). (A) Schematic representation of Rho family of small GTPases (Rho GTPases) signaling cascades involved in synaptic plasticity. Rho guanine-nucleotide exchange factor 11 (ARHGEF11) interacts and colocalizes with synapse marker postsynaptic density protein 95 (PSD-95) at synapse sites and negatively regulated the formation of dendritic spines in cortical primary neurons (Mizuki et al., 2016). Disrupted-in-schizophrenia 1 (DISC1) directly interacts with PSD-95 and kalirin-7, a GEF for Rac1, and blocks access of kalirin-7 to Rac1. This binding is released by N-methyl-D-aspartate (NMDA) receptor activation, allowing free access of kalirin-7 to Rac1 and leading to the resultant activation of Rac1 and spine enlargement (Hayashi-Takagi et al., 2010). (B) The role of Rho GTPase in pancreatic β cells. Rac1 is particularly important for glucose-stimulated insulin secretion (Wang and Thurmond, 2009). In contrast, RhoA expression is increased in β-cells under diabetic conditions, and Rho/Rho-kinase activation is involved in the suppression of insulin biosynthesis (Nakamura et al., 2006). Insulin release from pancreatic islet β-cells could be determined by the resulting balance of Rho GTPase signaling. Illustrating this schematic figure, we referenced figures of Hayashi-Takagi et al., 2010 and Wang et al., 2009.