Figure 5.

Simplified diagram depicts maturation and secretory pathway of insulin secretory granules in wild-type mouse pancreatic islet β-cells. In Step 1, proinsulin is packaged into vesicles that bud off from trans-Golgi network as immature secretory granules. In Step 2, the pH of immature granules is lowered facilitating action of prohormone convertases, which begin to cleave the soluble C-peptide chain from proinsulin, which is evidenced by the presence of clear, narrow halos. In Step 3, action of the prohormone convertases proceeds rapidly (as evident by relatively few granules with narrow halos), and the secretary granules become mature, displaying crystalline cores of insulin. In Step 4, mature granules fuse with the plasma membrane, release insulin to the extracellular space, and the membrane is recycled through clathrin-mediated endocytosis. The granules are then sorted for biphasic release, in which granules fuse to the membrane and release their contents.