18.14:
Insulin Secretory Vesicles
Increases in blood glucose stimulate pancreatic beta-islet cells to synthesize proinsulin, an insulin precursor. Newly synthesized proinsulin enters the trans-Golgi network, where it is present in a diffuse form inside immature secretory vesicles.
As the vesicles fuse together and mature, enzymes cleave proinsulin to form active insulin, which concentrates inside the vesicles, forming dense core vesicles.
High blood glucose also causes a glucose-induced calcium influx through a calcium channel. Calcium triggers a signaling cascade that eventually activates protein kinase C or PKC.
PKC enables reorganization of the actin network inside the cell to translocate the insulin containing secretory vesicles. The secretory vesicle then fuses with the plasma membrane to release large amounts of insulin in response to the increased blood glucose.
18.14:
Insulin Secretory Vesicles
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of voltage-gated calcium channels. Calcium enters the cell and triggers the docking, priming, and fusion of the insulin secretory vesicles with the plasma membrane for insulin release.
Insulin secretory vesicles follow the "kiss-and-run" model of exocytosis. In this model, when a secretory vesicle fuses with the plasma membrane, it opens a fusion pore to release insulin, closes the pore, and returns to the cytoplasm. The released insulin stimulates glucose uptake by cells and suppresses gluconeogenesis– new glucose formation by the liver.
Hormonal and neuronal signals regulate insulin secretion from β-islet cells. Molecules regulating insulin secretion include epinephrine, acetylcholine, and somatostatin. Defects in the biogenesis of insulin secretory vesicles, their fusion with the plasma membrane, or the exocytosis of insulin can lead to diabetes mellitus.
Suggested Reading
- Gunton, J., & Girgis, C. M. (2012). Pancreatic beta-cell failure in the pathogenesis of type 2 diabetes. Sydney University Press.
- Rutter, G. A., & Hill, E. V. (2006). Insulin vesicle release: walk, kiss, pause… then run. Physiology, 21(3), 189-196.
- MacDonald, P. E., & Rorsman, P. (2007). The ins and outs of secretion from pancreatic β-cells: control of single-vesicle exo-and endocytosis. Physiology, 22(2), 113-121.