insulinvesikler

Insulin vesicles, also known as insulin secretory granules, are specialized, dense-core organelles located in pancreatic beta cells. They store the hormone insulin together with C-peptide and other components such as zinc and islet amyloid polypeptide (amylin) until secretion is triggered by nutrient signals. The vesicles are positioned near the plasma membrane to support rapid release in response to meals.

Biogenesis and composition: Insulin vesicles form in the endoplasmic reticulum as proinsulin and are transported to the trans-Golgi network, where they are packaged with chromogranin A and other granule contents. In the granule lumen, proinsulin is cleaved by prohormone convertases PC1/3 and PC2 to mature insulin and C-peptide. The granule lumen is acidic and zinc is co-packaged, stabilizing insulin as hexamers that can be readily mobilized for secretion.

Secretion mechanism: In response to elevated blood glucose, beta-cell metabolism increases the ATP/ADP ratio, leading to closure of KATP channels and membrane depolarization. This opens voltage-gated calcium channels, allowing a rise in intracellular calcium that triggers SNARE-mediated fusion of insulin vesicles with the plasma membrane. Secretion occurs from distinct vesicle pools, including a readily releasable pool and a larger reserve pool, and is tightly regulated by exocytotic proteins such as syntaxin-1, SNAP-25, and synaptotagmin-7, along with priming factors like Munc18 and Munc13.

Clinical relevance: Proper trafficking and exocytosis of insulin vesicles are essential for first-phase insulin secretion; defects contribute to beta-cell dysfunction observed in type 2 diabetes and other disorders. C-peptide measurements reflect endogenous insulin secretion and are used clinically to assess beta-cell function. Research on vesicle maturation, docking, and the roles of zinc and islet amyloid polypeptide continues to advance understanding of insulin release.