Although there is evidence indicating transcriptional and functional heterogeneity in human beta cells, it is unclear whether this heterogeneity extends to the expression level of the enzymes that process proinsulin to insulin in beta cells. To address this question, the expression levels of prohormone convertases (PC) 1/3, proprotein convertase 2 (PC2), and carboxypeptidase E (CPE) were determined in immune-stained sections of human pancreas. In non-diabetic donors, the level of proprotein convertase 1/3 (PC1/3) expression varied among beta cells of each islet but the average per islet was similar for all islets of each donor. Although the average PC1/3 expression of all islets examined per sample was unique for each pancreas, donors had similar levels of proinsulin/insulin expression. PC2 expression in beta cells showed less pronounced inter- and intraislet variation while CPE levels were fairly constant. The relationship between PC1/3 and PC2 expression levels was variable among different donors. Type 2 diabetes had an uneven effect on the expression levels of all three enzymes as they decrease only in some islets in a section. These findings suggest the presence of intraislet, but not interislet, variation in the expression of the proinsulin processing enzymes in non-diabetic subjects and a heterogeneous effect of type 2 diabetes on enzyme expression in islets.

中文翻译：

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非胰岛素和2型糖尿病人的β细胞中胰岛素原加工酶的异质表达。

尽管有证据表明人类β细胞存在转录和功能异质性，但尚不清楚这种异质性是否扩展到β细胞中将胰岛素原转化为胰岛素的酶的表达水平。为了解决这个问题，在人胰腺的免疫染色切片中测定了激素原转化酶（PC）1/3，原蛋白转化酶2（PC2）和羧肽酶E（CPE）的表达水平。在非糖尿病供体中，每个胰岛的β细胞之间的前蛋白转化酶1/3（PC1 / 3）表达水平不同，但是每个供体的所有胰岛的每个胰岛的平均值相似。尽管每个样品检查的所有胰岛的平均PC1 / 3表达对于每个胰腺都是唯一的，但供体的胰岛素原/胰岛素表达水平相似。β细胞中PC2的表达显示出较小的胰岛间和胰岛内变异，而CPE水平则相当恒定。PC1 / 3和PC2表达水平之间的关系在不同的供体之间是可变的。2型糖尿病对这三种酶的表达水平影响不均，因为它们仅在部分胰岛中降低。这些发现表明在非糖尿病受试者中存在胰岛内而不是胰岛间胰岛素原加工酶表达的变化，以及2型糖尿病对胰岛中酶表达的异质作用。2型糖尿病对这三种酶的表达水平影响不均，因为它们仅在部分胰岛中降低。这些发现表明在非糖尿病受试者中存在胰岛内而不是胰岛间胰岛素原加工酶表达的变化，以及2型糖尿病对胰岛中酶表达的异质作用。2型糖尿病对这三种酶的表达水平影响不均，因为它们仅在部分胰岛中降低。这些发现表明在非糖尿病受试者中存在胰岛内而不是胰岛间胰岛素原加工酶表达的变化，以及2型糖尿病对胰岛中酶表达的异质作用。