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Title

The intracellular handling of insulin-related peptides in isolated pancreatic islets. Evidence for differential rates of degradation of insulin and C-peptide

Authors
Rhodes, C. J.
Published in Biochemical Journal. 1988, vol. 251, no. 1, p. 23-30
Abstract Islets of Langerhans isolated from adult rats were maintained in tissue culture for 3 days in the continued presence of [3H]leucine. Labelled proinsulin, C-peptide and insulin were measured by quantitative h.p.l.c., a method which also allowed for resolution of C-peptide I and II, and of insulin I and II (the products of the two rat insulin genes). The results showed that: (1) at early times, proinsulin was the major radiolabelled product; with progressive time in culture, intra-islet levels of [3H]proinsulin decreased, despite continuous labelling with [3H]leucine, indicating that the combined rates of proinsulin conversion into insulin and of proinsulin release, exceeded the rate of synthesis; (2) insulin I levels were always greater than those of insulin II, both in the islets and for products released to the medium; (3) the molar ratio of [3H]insulin I and II to their respective 3H-labelled C-peptides increased with time for products retained within islets, reaching a value close to 3:1 by 3 days; by contrast, for products released to the medium during the culture period, the ratio was always close to unity; (4) when islets were incubated with [3H]leucine for 2 days, and then left for a further 1 day without label (chase period), the intra-islet [3H]insulin/[3H]C-peptide ratios rose to values as high as 9:1. Again, for material released to the medium, the values were close to 1:1; (5) it is concluded that C-peptide is degraded more rapidly than insulin within islet cells, thereby accounting for the elevated insulin/C-peptide ratios. The difference between the ratios observed in the islets and those for material released to the medium is taken to indicate that degradation occurs in a discrete cellular compartment and not in the secretory granule itself.
Keywords AnimalsC-Peptide/ metabolismCells, CulturedChromatography, High Pressure LiquidInsulin/ metabolismIntracellular Fluid/metabolismIslets of Langerhans/ metabolismLeucine/metabolismMaleProinsulin/metabolismRadioimmunoassayRatsRats, Inbred Strains
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PMID: 3291861
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RHODES, C. J., HALBAN, Philippe A. The intracellular handling of insulin-related peptides in isolated pancreatic islets. Evidence for differential rates of degradation of insulin and C-peptide. In: Biochemical Journal, 1988, vol. 251, n° 1, p. 23-30. https://archive-ouverte.unige.ch/unige:8992

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Deposited on : 2010-07-12

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