Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.
J Clin Endocrinol Metab. 2017 Jul 1;102(7):2595-2603. doi: 10.1210/jc.2016-2773.
Islet amyloid is a feature of β-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in β cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in β-cell prohormone processing.
Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes.
DESIGN, SETTING, AND PATIENTS: We developed an immunoassay to detect proIAPP1-48 in human plasma, and we determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls.
The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 <15%. Healthy individuals had plasma concentrations of proIAPP1-48 immunoreactivity of 1.5 ± 0.2 pM and a proIAPP1-48 to total IAPP ratio of 0.28 ± 0.03. Plasma concentrations of proIAPP1-48 immunoreactivity were not significantly different in subjects with T2D but were markedly increased in T1D recipients of islet transplants. Children and adults with T1D had reduced mature IAPP levels relative to age-matched controls but an elevated ratio of proIAPP1-48 to total IAPP.
The β cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP1-48-to-IAPP immunoreactivity may have value as a biomarker of β-cell stress and dysfunction.
胰岛淀粉样变是 2 型糖尿病（T2D）和胰岛移植的 1 型糖尿病（T1D）患者β细胞衰竭的一个特征。胰岛淀粉样包含胰岛淀粉样多肽（IAPP；胰岛素原），这是一种在β细胞中由其前体，前胰岛素原 1-67，通过中间形式，前胰岛素原 1-48，加工产生的循环肽。糖尿病患者血浆中升高的胰岛素原与 C 肽比值表明β细胞前激素加工缺陷。
确定糖尿病患者血浆中 IAPP 前体形式的水平是否升高。
设计、设置和患者：我们开发了一种免疫测定法来检测人血浆中的前胰岛素原 1-48，并确定 T1D、T2D、胰岛移植受者和健康对照者中前胰岛素原 1-48 与成熟 IAPP 的比值。
前胰岛素原 1-48 免疫测定的检测限为 0.18±0.06 pM，与完整的前胰岛素原 1-67 的交叉反应性<15%。健康个体的前胰岛素原 1-48 免疫反应性血浆浓度为 1.5±0.2 pM，前胰岛素原 1-48 与总 IAPP 的比值为 0.28±0.03。T2D 患者的前胰岛素原 1-48 免疫反应性血浆浓度没有显著差异，但胰岛移植的 T1D 受者明显升高。T1D 的儿童和成人与年龄匹配的对照组相比，成熟 IAPP 水平降低，但前胰岛素原 1-48 与总 IAPP 的比值升高。
T1D 和胰岛移植中的β细胞前胰岛素原 1-48 中间处理受损。前胰岛素原 1-48 与 IAPP 免疫反应性的比值可能作为β细胞应激和功能障碍的生物标志物具有价值。
