Sécrétion d'insuline : parcours intracellulaire et cheminement extracellulaire

Abstract

Insulin and C-peptide have been revealed by immunocytochemistry in the pancreatic tissue. Combination of good ultrastructural preservation leading to immunolabelings of high resolution with quantitative evaluations, has permitted to follow the journey of insulin along the cellular compartments of the B-cell involved in secretion as well as along its extracellular path, revealing interactions of the secreted insulin with various pancreatic cells. In B-cells the pre-pro-insulin is synthesized in the rough endoplasmic reticulum, and the pro-insulin is transferred to the Golgi apparatus. Immature secretory granules originating from the Golgi saccules concentrate the pro-insulin, convert it to insulin and C-peptide and along with maturation move them towards the plasma membrane for discharge. Outside the cell, insulin diffuses through the interstitial space and interacts with binding sites located in the lateral membrane of the B-cell itself and with other cells including non-B endocrine cells, acinar cells and the endothelial cells. Insulin appears to traverse the capillary wall through two routes, the endothelial pores and the trans-endothelial vesicular system. A quantitative evaluation has revealed the rapid dilution of insulin as it travels through the interstitial space and the blood vessels. Cells present along the extracellular pathway are thus exposed to variable levels of insulin which influence differently their behavior. This is particularly true for the acinar cells which have been divided into two subpopulations according to their topographical location. In addition to their presence in the islets of Langerhans, B-cells were also revealed in the epithelial lining of the pancreatic duct system. These cells are of the << open >> type and have the capability of an << exocrine >> secretion of insulin into the pancreatic juice. A paracrine influence of the insulin conveyed by the pancreatic juice, upon the duct and intestinal epithelia has been suggested. Thus, the secretory pathway as well as the extracellular route of insulin, as revealed by high resolution immunocytochemistry, demands reevaluation for a better understanding of problems occurring in diabetes.