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Scientific article
English

Kinetics of proinsulin conversion in human islets

Published inDiabetes, vol. 42, no. 6, p. 933-936
Publication date1993
Abstract

Islets isolated from human cadaver pancreas were pulse-labeled (10 min with [3H]leucine) and then incubated for a 180-min chase. Islets and chase medium were collected every 15 min and analyzed by reversed-phase HPLC to quantify the percentage of radioactively labeled proinsulin, conversion intermediates, and fully processed insulin. Release of proinsulin-related labeled products into the chase medium was < 10% of total. Whereas 50% of labeled proinsulin had been lost by conversion within 45 min, fully processed insulin only appeared with a half-time of 100 min. This discrepancy is attributable to accumulation of radioactive conversion intermediates. Des 64.65 split proinsulin was a minor component, reaching a maximum of 5.2 +/- 1.7% (n = 4) at 60 min of chase. By contrast, des 31.32 split proinsulin--and a truncated form lacking the first three residues of C-peptide--rose progressively to 29.3 +/- 1.4% by 75 min, and declined thereafter. The accumulation of des 31.32 split proinsulin rather than the des 64.65 split form during the conversion of human proinsulin reflects slower conversion at the C-peptide/A-chain than at the B-chain/C-peptide junction, and is consistent with the appearance of this particular conversion intermediate in the circulation.

Keywords
  • Adult
  • Amino Acid Sequence
  • C-Peptide/metabolism
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Insulin/metabolism
  • Islets of Langerhans/ metabolism
  • Kinetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Proinsulin/ metabolism
  • Time Factors
Citation (ISO format)
SIZONENKO, Stéphane et al. Kinetics of proinsulin conversion in human islets. In: Diabetes, 1993, vol. 42, n° 6, p. 933–936.
Identifiers
ISSN of the journal0012-1797
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