INSULIN-SECRETION - INTRACELLULAR PATHWAY AND EXTRACELLULAR ROUTE

Insulin and C-peptide have been revealed by immunocytochemistry in the pancreatic tissue. Combination of good ultrastructural preservation l eading to immunolabelings of high resolution with quantitative evaluat ions, has permitted to follow the journey of insulin along the cellula r compartments of the B-cell involved in secretion as well as along it s extracellular path, revealing interactions of the secreted insulin w ith various pancreatic cells. In B-cells the pre-pro-insulin is synthe sized in the rough endoplasmic reticulum, and the pro-insulin is trans ferred to the Golgi apparatus. Immature secretory granules originating from the Golgi saccules concentrate the pro-insulin, convert it to in sulin and C-peptide and along with maturation move them towards the pl asma membrane for discharge. Outside the cell, insulin diffuses throug h the interstitial space and interacts with binding sites located in t he lateral membrane of the B-cell itself and with other cells includin g non-B endocrine cells, acinar cells and the endothelial cells. Insul in appears to traverse the capillary wall through two routes, the endo thelial pores and the trans-endothelial vesicular system. A quantitati ve evaluation has revealed the rapid dilution of insulin as it travels through the interstitial space and the blood vessels. Cells present a long the extracellular pathway are thus exposed to variable levels of insulin which influence differently their behavior. This is particular ly true for the acinar cells which have been divided into two subpopul ations according to their topographical location. In addition to their presence in the islets of Langerhans, B-cells were also revealed in t he epithelial lining of the pancreatic duct system. These cells are of the << open >> type and have the capability of an << exocrine >> secr etion of insulin into the pancreatic juice. A paracrine influence of t he insulin conveyed by the pancreatic juice, upon the duct and intesti nal 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 o f problems occurring in diabetes.