Figure 5

Glucose control of insulin translation. Glucose stimulates insulin synthesis largely by promoting insulin translation initiation. (1) Glucose promotes the phosphorylation of eIF-4EBP and activates eIF-4E; eIF-4E, eIF-4A and eIF-4G form eIF-4F, a complex whose functions include recognition of preproinsulin mRNA and recruiting 40S ribosome to mRNA. (2) eIF2 is a critical factor regulating protein biosynthesis. It is active only in GTP-bound state. A factor named eIF-2B functions to convert GDP-bound eIF-2 to GTP-bound eIF-2. The activity of eIF-2B is transiently up-regulated after glucose stimulation. Additionally, phosphorylation of alpha subunit of eIF2 (eIF2α) inhibits the formation of eIF2-GTP·Met-tRNAi translational ternary complex, which binds 40S ribosome and is indispensable for protein translation. Glucose causes the dephosphorylation of eIF2α, and induces an increase in the availability of the translational ternary complex.