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Kinetics of proinsulin conversion in human islets

Irminger, J. C.
Morel, P.
Published in Diabetes. 1993, vol. 42, no. 6, p. 933-936
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 AdultAmino Acid SequenceC-Peptide/metabolismChromatography, High Pressure LiquidFemaleHumansInsulin/metabolismIslets of Langerhans/ metabolismKineticsMaleMiddle AgedMolecular Sequence DataProinsulin/ metabolismTime Factors
PMID: 8495816
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SIZONENKO, Stéphane et al. Kinetics of proinsulin conversion in human islets. In: Diabetes, 1993, vol. 42, n° 6, p. 933-936. https://archive-ouverte.unige.ch/unige:9260

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