Fig. 4

Regulation of GCK activity in pancreatic β-cells. In pancreatic β-cells, GCK activity is regulated by several binding partners: (1) GCK activity can be inhibited when it binds to insulin granules. The interaction between GCK and insulin granules is partly mediated by NOS. To reverse this interaction and stimulate GCK activity, NOS performs S-nitrosylation of GCK. (2) PFK-2/ FBPase-2. The regulation of GCK by PFK-2/ FBPase-2 involves direct binding of GCK and activation, depending on the phosphorylation status of FBPase-2. (3) Activation of GCK occurs via the BAD protein at the mitochondrial membrane. When phosphorylated at the BH3 domain, BAD binds to GCK near its active site, leading to GCK activation and subsequent insulin secretion. Furthermore, the interaction between BAD and GCK can provide protection against apoptosis