Halban P A, Mutkoski R, Dodson G, Orci L
Diabetologia. 1987 May;30(5):348-53. doi: 10.1007/BF00299029.
Insulin is thought to be chemically stabilized within beta-granules in the crystal form. The other major products of the beta-granule, proinsulin and C-peptide, by contrast, are not thought able to crystallize. The physico-chemical properties of peptides in soluble or crystalline form are dramatically different. The ability of insulin to crystallize in the beta-granule might thus explain why this peptide, but not proinsulin/C-peptide, remains stable even after its introduction into lysosomes as occurs during granulolysis (crinophagy). We have now studied this by exposing proinsulin or insulin to lysosomal proteases in vitro. 125I-insulin in soluble form was found to be degraded at the same rate as 125I-proinsulin. Strikingly, however, when the labelled insulin was crystallized, its rate of degradation was decreased from 1.9 to 0.2 pmol/min. We take these data as confirmation that the insulin crystal is resistant to degradation, thereby possibly accounting for (a) the presence of insulin immunoreactivity within multigranular bodies, and (b) the unusually slow rate of degradation of insulin within B cells compared with that of other hormones in their cells of origin.
胰岛素被认为在β颗粒内以晶体形式化学稳定。相比之下，β颗粒的其他主要产物胰岛素原和C肽则被认为不能结晶。肽以可溶或晶体形式存在时，其物理化学性质有很大差异。胰岛素在β颗粒中结晶的能力因此可以解释为什么这种肽，而不是胰岛素原/C肽，即使在颗粒溶解（自噬性溶酶体消化）过程中被引入溶酶体后仍保持稳定。我们现在通过在体外将胰岛素原或胰岛素暴露于溶酶体蛋白酶来研究这一问题。发现可溶形式的125I-胰岛素与125I-胰岛素原以相同的速率降解。然而，引人注目的是，当标记的胰岛素结晶时，其降解速率从1.9皮摩尔/分钟降至0.2皮摩尔/分钟。我们将这些数据视为胰岛素晶体抗降解的证据，这可能解释了（a）多颗粒体内胰岛素免疫反应性的存在，以及（b）与其他激素在其起源细胞中的降解速率相比，B细胞内胰岛素降解速率异常缓慢的原因。
