Differential Rates of Release of Newly Synthesized and of Stored Insulin from Pancreatic Islets*

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Abstract
Rat pancreatic islets were maintained in tissue culture (8.3 mM glucose) for 3 days in the presence of [3H]leucine in order to label insulin stores. Alternatively, islets were labeled for 1 h at the end of a 3-day maintenance period in order to label only newly synthesized insulin. During a 24-h chase incubation, 13% of the prelabeled insulin stores (3-day label) had been released. By contrast, 30% of newly synthesized (1-h label) insulin was released during a similar chase period. Since islets were handled identically aside from the respective time of exposure to [3H]leucine, the total immunoreactive islet insulin content and that released into the medium was similar for both groups of islets. The specific radioactivity of the labeled insulin in the medium at the end of the chase period was thus lower than that remaining in the islets for islets prelabeled for 3 days but was higher after the labeling of newly synthesized insulin for 1 h. When the rate of newly synthesized insulin was followed during a 4-h chase period at 8.3 mM glucose, it was found that the specific radioactivity of the labeled insulin released into the medium was 250% that found in the islets at the start of the chase. Such isotopic enrichment of labeled insulin in the medium indicates the preferential release of newly synthesized (labeled) insulin under these conditions. By contrast, when insulin release was stimulated (16.7 mM glucose or 1 mM 3-isobutyl-1-methylxanthine at 2.8 mM glucose), there was less marked isotopic enrichment of released labeled insulin, indicating that under these conditions there was no longer pronounced preferential release of newly synthesized insulin. The results suggest that islets contain at least two labile pools of insulin which display differential sensitivity towards secretagogues. This could result from either heterogeneity among β- granules or β-cells.