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Scientific article
English

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

Published inThe Journal of biological chemistry, vol. 268, no. 22, p. 16248-16252
Publication date1993
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
  • Animals
  • C-Peptide/ metabolism
  • Chromatography, High Pressure Liquid
  • Cytoplasmic Granules/metabolism
  • Humans
  • Islets of Langerhans/cytology/ metabolism
  • Kinetics
  • Lysosomes/metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Cells, Cultured
Citation (ISO format)
NEERMAN ARBEZ, Marguerite, HALBAN, Philippe A. Novel, non-crinophagic, degradation of connecting peptide in transformed pancreatic beta cells. In: The Journal of biological chemistry, 1993, vol. 268, n° 22, p. 16248–16252.
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ISSN of the journal0021-9258
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