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Abstract Proinsulin is a single polypeptide chain composed of the B and A subunits of insulin joined by the C-peptide region. Vesicles and cisternae in the trans Golgi apparatus of human fibroblasts are acidic compartments. Visualization of acidic organelles in intact cells by electron microscopy. Recycling receptors: the round-trip itinerary of migrant membrane proteins. ATP-driven proton fluxes across membranes of secretory organelles. J Biol Chem.
Post-translational proteolysis in polypeptide hormone biosynthesis. Annu Rev Physiol. Conversion of proinsulin to insulin: involvement of a 31, molecular weight thiol protease. Characterization of the ATP-dependent proton pump of clathrin-coated vesicles.
Clathrin-coated vesicles contain an ATP-dependent proton pump. Acidification of macrophage and fibroblast endocytic vesicles in vitro. The internal pH and membrane potential of the insulin-secretory granule. Biochem J. Method for the isolation of intact islets of Langerhans from the rat pancreas. Am J Physiol. The production and characterization of monoclonal antibodies specific for human proinsulin using a sensitive microdot assay procedure.
Human proinsulin-specific antigenic determinants identified by monoclonal antibodies. Two rapid and simple methods used for the removal of resins from 1. J Microsc. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents.
Identification and characterization of a proton pump on lysosomes by fluorescein-isothiocyanate-dextran fluorescence. Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts.
A clathrin-coated, Golgi-related compartment of the insulin secreting cell accumulates proinsulin in the presence of monensin. Direct identification of prohormone conversion site in insulin-secreting cells. Insulin, not C-peptide proinsulin , is present in crinophagic bodies of the pancreatic B-cell. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm.
When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C peptide is also secreted into blood, but has no known biological activity. Insulin is secreted in primarily in response to elevated blood concentrations of glucose.
This makes sense because insulin is "in charge" of facilitating glucose entry into cells. Some neural stimuli e. Our understanding of the mechanisms behind insulin secretion remain somewhat fragmentary. Nonetheless, certain features of this process have been clearly and repeatedly demonstrated, yielding the following model:. Stimulation of insulin release is readily observed in whole animals or people. The normal fasting blood glucose concentration in humans and most mammals is 80 to 90 mg per ml, associated with very low levels of insulin secretion.
The figure to the right depicts the effects on insulin secretion when enough glucose is infused to maintain blood levels two to three times the fasting level for an hour.
Almost immediately after the infusion begins, plasma insulin levels increase dramatically. This initial increase is due to secretion of preformed insulin, which is soon significantly depleted.
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