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Novel, non-crinophagic, degradation of connecting peptide in transformed pancreatic beta cells

Published in Journal of Biological Chemistry. 1993, vol. 268, no. 22, p. 16248-16252
Abstract Proinsulin is converted to equimolar amounts of insulin and connecting peptide (C-peptide) in pancreatic beta cell secretory granules. The fate of C-peptide, which remains soluble in granules while insulin is crystallized, was studied in a rat insulinoma cell line (INS cells). A pulse-chase approach demonstrated that insulin to C-peptide ratios (I/CP) began to rise in INS cells as soon as conversion took place, reaching 2.2:1 at 6 h of chase, and 5.3:1 by 24 h. During the first 4 h of chase, this ratio was inverted in the medium under basal conditions, possibly reflecting preferential secretion of C-peptide via the post granular constitutive-like pathway. However, the amount of C-peptide secreted to the medium (1.4%/h) was trivial compared with the net loss of C-peptide from the INS cells, estimated to be approximately 33% during the 1st h. As no extracellular degradation of insulin or C-peptide was observed, the data show progressive, extensive intracellular degradation of C-peptide. Stimulation of INS granule exocytosis revealed that the I/CP ratio in secretory granules is representative of that of cell extracts, indicating that C-peptide, but not insulin, is lost from functionally competent granules with time. This particular degradative route for C-peptide is thus distinct from crinophagy (fusion of granules and lysosomes) and was found to be much more active in INS cells than in primary islet beta cells.
Keywords AnimalsC-Peptide/ metabolismChromatography, High Pressure LiquidCytoplasmic Granules/metabolismHumansIslets of Langerhans/cytology/ metabolismKineticsLysosomes/metabolismMaleRatsRats, Sprague-DawleyTumor Cells, Cultured
PMID: 8344910
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NEERMAN ARBEZ, Marguerite, HALBAN, Philippe A. Novel, non-crinophagic, degradation of connecting peptide in transformed pancreatic beta cells. In: Journal of Biological Chemistry, 1993, vol. 268, n° 22, p. 16248-16252. https://archive-ouverte.unige.ch/unige:8933

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Deposited on : 2010-07-12

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