Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York.
J Histochem Cytochem. 2019 Jun;67(6):385-400. doi: 10.1369/0022155419831641. Epub 2019 Feb 13.
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.
尽管有证据表明人类β细胞存在转录和功能异质性，但β细胞中加工胰岛素原的酶的表达水平是否存在这种异质性尚不清楚。为了解决这个问题，我们测定了人胰腺免疫染色切片中前激素转化酶（PC）1/3、蛋白水解酶 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β细胞中 PC1/3 的表达水平存在差异，但每个供体的所有胰岛的平均水平相似。尽管每个样本中所有胰岛的 PC1/3 表达平均水平对每个胰腺都是独特的，但供体的胰岛素原/胰岛素表达水平相似。PC2 在β细胞中的表达显示出较小的岛间和岛内变异，而 CPE 水平则相当稳定。PC1/3 和 PC2 表达水平之间的关系在不同供体之间存在差异。2 型糖尿病对所有三种酶的表达水平产生不均匀的影响，因为它们仅在切片中的一些胰岛中降低。这些发现表明，在非糖尿病个体中，胰岛素原加工酶的表达存在岛内但不存在岛间的变异，并且 2 型糖尿病对胰岛中酶表达的影响具有异质性。
