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- Title
Kinetics of proinsulin conversion in human islets.
- Authors
Sizonenko, Stéphane; Irminger, Jean-Claude; Buhler, Léo; Shaoping Deng; Morel, Philippe; Halban, Philippe A.; Sizonenko, S; Irminger, J C; Buhler, L; Deng, S; Morel, P; Halban, P A
- 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.
- Publication
Diabetes, 1993, Vol 42, Issue 6, p933
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diab.42.6.933