Mechanism of Insulin Exocytosis Analyzed by Imaging Techniques

Abstract

Insulin is synthesized in rough endoplasmic reticulum (RER), delivered to the secretory granules where it is processed from proinsulin to insulin, stored, and released by the mechanism of exocytosis. Insulin release in vivo must be controlled minute by minute in order to maintain blood glucose levels within a narrow physiological range. The regulation of insulin exocytosis is critical to fine control of glucose homeostasis. Insulin exocytosis consists of several steps, including docking, priming, and final fusion with the plasma membrane. Fundamental components of secretory machinery such as soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor (SNARE) play an important role in insulin exocytosis. Recently, several new techniques such as capacitance measurements, confocal, two-photon and total internal reflection fluorescence (TIRF) microscopy have been applied to study insulin exocytosis. In particular, these new imaging techniques are powerful tools for addressing the mechanism of insulin exocytosis and examining the relationship between docking and fusion of granules and proteins implicated in the secretory machinery. This review focuses on the molecular mechanism of insulin exocytosis analyzed by the TIRF imaging system.