CBS and Hyperglycemia: Kundu et al. (2013) showed that MMP-9 was upregulated in Akita diabetic mice along with the reduction of CBS and CSE. When MMP-9 is knocked out, the expression of the two H2S producing enzyme namely CSE and CBS shows a trend toward baseline despite hyperglycemia (Kundu et al., 2013) suggesting that MMP-9 regulates CBS and CSE expression in DN (Figure 3A).