There Is Something About Insulin Granules

Insulin secretory granules of pancreatic β-cells are complex intracellular organelles comprising many proteins with different catalytic activities and messenger functions (1). These subcellular organelles have a distinctive morphology in electron micrographs as a sphere of around 200–300 nm in diameter comprising a crystalline core of insulin surrounded by a halo of less dense material in a phospholipid bilayer envelope (Fig. 1) (2). The granule is more than just a hormone repository in the cell. It is the site of proteolytic conversion of proinsulin into insulin. This dynamic structure is also involved in intercellular transport and communication through the secretion of other biologically active molecules. Around 10% of the granule population turns over every hour during active secretion. An important contribution to our understanding of the regulation of insulin secretion has come from studies of the granules, and in particular the elucidation of the structure and function of many granule proteins (1). Figure 1 Multitasking by insulin granules. Insulin secretory granules (right) are unique features of β-cells (green; left) in pancreatic islets. Light organelles represent immature granules, whereas mature granules are dark and dense spheres containing insulin crystals, which are distinct from somatostatin granules in delta cells (blue). Native proteins as well as posttranscriptionally or posttranslationally modified proteins and sphingolipids have now been identified in these characteristic organelles that act as autoantigenic targets or immune modulators of islet-specific autoreactive CD4 and CD8 T cells. (Electron microscopy graph kindly shared by Dr. Ben Giepmans [2].) But there is something else …