A review on insulin trafficking and exocytosis

Insulin is a peptide hormone responsible for stable glycemia, is entirely secreting from pancreatic β cells at the core of glucose homeostatic regulation. Upon synthesis as preproinsulin on rough endoplasmic reticulum (rER), proinsulin is directed to trans Golgi apparatus. Subsequently, proinsulin packaging into secretory granules occurs in a dynamic and highly efficient process. During maturation stage of secretory granules, proinsulin undergoes cleavage and produces insulin and C-peptide upon acidification of the granules due to the activation of ATP-deriven proton pump. Fusion of the insulin containing secretory granules with the plasma membranes takes place after an increase in intracellular Ca²⁺. Finally, insulin is co-secreting with other components that are present in the secretory granules, including C-peptide, ATP, γ-aminobutyric acid (GABA), ghrelin and amylin. The other accompanying components of the insulin vesicles play important roles in the insulin secretion, insulin receptor activation and other homeostatic effects.. Responding to the glucose stimulation or increases in cytoplasmic Ca²⁺ levels, insulin secretion is immediately starts. Whereas, the second phase of insulin secretion is slow and continued, which reaches a plateau within 1-3 hours and lasts for longer period. In contrast to the first phase, the second phase of insulin secretion is independent of the extracellular glucose level. Finally, sequential or compound exocytosis of insulin is repressed to prevent sugar crash arising from excessive and sudden insulin secretion. In this paper we have reviewed the recent progress of molecular scenarios which are behind insulin biogenesis, intracellular sorting and exocytosis events.