In pancreatic beta cells, proinsulin (ProIN) undergoes folding in endoplasmic reticulum/Golgi system and is translocated to secretory vesicles for processing into insulin and C-peptide by the proprotein convertases (PC)1/3 and PC2, and carboxypeptidase E. Human beta cells show significant variation in the level of expression of PC1/3, the critical proconvertase involved in proinsulin processing. To ascertain whether this heterogeneity is correlated with the level of expression of the prohormone and mature hormone, the expression of proinsulin, insulin, and PC1/3 in human beta cells was examined. This analysis identified a human beta cell type that expressed proinsulin but lacked PC1/3 (ProIN⁺PC1/3⁻). This beta cell type is absent in rodent islets and is abundant in human islets of adults but scarce in islets from postnatal donors. Human islets also contained a beta cell type that expressed both proinsulin and variable levels of PC1/3 (ProIN⁺PC1/3⁺) and a less abundant cell type that lacked proinsulin but expressed the convertase (ProIN⁻PC1/3⁺). These cell phenotypes were altered by type 2 diabetes. These data suggest that these three cell types represent different stages of a dynamic process with proinsulin folding in ProIN⁺PC1/3⁻ cells, proinsulin conversion into insulin in ProIN⁺PC1/3⁺cells, and replenishment of the proinsulin content in ProIN⁻PC1/3⁺ cells:

在胰腺 β 细胞中，胰岛素原 (ProIN) 在内质网/高尔基体系统中发生折叠，并被转移到分泌囊泡，以通过前蛋白转化酶 (PC)1/3 和 PC2 以及羧肽酶 E 加工成胰岛素和 C 肽。细胞表现出 PC1/3 表达水平的显着变化，PC1/3 是参与胰岛素原加工的关键转化酶原。为了确定这种异质性是否与激素原和成熟激素的表达水平相关，检查了人 β 细胞中胰岛素原、胰岛素和 PC1/3 的表达。该分析确定了一种表达胰岛素原但缺乏 PC1/3 (ProIN ⁺ PC1/3 ^-）。这种 β 细胞类型在啮齿动物胰岛中不存在，在成人的人类胰岛中含量丰富，但在出生后捐赠者的胰岛中却很少。人胰岛还包含表达胰岛素原和不同水平的 PC1/3 (ProIN ⁺ PC1/3 ⁺ )的 β 细胞类型和缺乏胰岛素原但表达转化酶 (ProIN ^- PC1/3 ⁺ )的较少细胞类型。这些细胞表型被 2 型糖尿病改变。这些数据表明，这三种细胞类型代表在PROIN胰岛素原折叠一个动态过程的不同阶段⁺ PC1 / 3 ^-细胞，胰岛素原转化为在PROIN胰岛素⁺ PC1 / 3 ⁺ProIN ^- PC1/3 ⁺细胞中胰岛素原含量的补充：