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S. OZAKI, N. KALANT, THE ROLE OF LYSOSOMES IN HEPATIC METABOLISM OF INSULIN, Endocrinology, Volume 112, Issue 1, 1 January 1983, Pages 381–383, https://doi.org/10.1210/endo-112-1-381
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We have studied the suitability of the insulin-receptor complex as a substrate for hepatic lysosomal and cytoplasmic insulin-degrading enzymes. Broken lysosome preparations degraded receptor-bound insulin more slowly than free insulin; most of the degradation of bound insulin could be accounted for by prior dissociation of the complex and degradation of the freed insulin. At pH 7.6 insulin showed rapid specific and nonspecific binding to intact lysosomes; no degradation products appeared in the medium. The associated insulin could be recovered by disrupting the lysosomes or by dissociation which was rapid and complete, particularly at low pH (5.5); in both cases more than 75% of the recovered insulin was intact. Insulin did not show specific binding to lysosomal membrane, suggesting that the insulin bound to intact lysosomes was intralysosomal. Free insulin but not receptor-bound insulin was rapidly degraded by cytosolic enzymes. It is hypothesized that if receptorbound insulin were introduced into lysosomes from endocytic vesicles it would be rapidly dissociated at the prevailing intralysosomal pH; most of the insulin would be rapidly released from the lysosomes and would be available for intracellular binding and for degradation by cytosolic insulin protease.
