Figure 2

Insulin synthesis and secretion process. After preproinsulin mRNA transcription, preproinsulin is synthesized in the ER and converted into proinsulin, proinsulin is transported through the Golgi apparatus and packaged into immature clathrin-coated granules, where proinsulin is processed into insulin and c-peptide. The immature granules can then become mature granules containing cystalized insulin. After glucose stimulation insulin granules exhibit two characteristic phases that consist of a rapidly initiated but transient first phase and a sustained second phase, because the granules are divided into two different pools. (1) A limited pool of granules (< 5%) ready for immediate release and is referred to as the "readily releasable pool" (RRP), which account for the first release phase. (2) Most of the granules (> 95%) belong to a reserve pool responsible for the second-phase of insulin secretion, granules in this pool must undergo mobilization before they can gain release competence.