Measurement of Pro-Islet Amyloid Polypeptide (1-48) in Diabetes and Islet Transplants

Measurement of Pro-Islet Amyloid Polypeptide (1-48) in Diabetes and Islet Transplants
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DOI:
10.1210/jc.2016-2773
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发表时间:
2017-07-01
影响因子:
5.8
通讯作者:
Verchere, C. Bruce
Verchere, C. Bruce
中科院分区:
医学2区
文献类型:
--
作者:
Courtade, Jaques A.;Klimek-Abercrombie, Agnieszka M.;Verchere, C. Bruce

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背景:胰岛淀粉样蛋白是2型糖尿病(T2 D)和1型糖尿病(T1 D)胰岛移植受体β细胞衰竭的特征。胰岛淀粉样蛋白含有胰岛淀粉样蛋白多肽(IAPP;胰淀素),这是一种循环肽,通过其前体proIAPP(1-67)经中间形式proIAPP(1-48)加工而在β细胞中产生。糖尿病患者血浆中胰岛素原与C肽比值升高提示β细胞激素原加工缺陷。目的:确定糖尿病患者血浆中IAPP前体形式水平是否升高。设计、设置和患者:我们开发了一种检测人血浆中proIAPP(1-48)的免疫测定法,并测定了T1 D、T2 D、T2 D和T2 D受试者中proIAPP(1-48)与成熟IAPP的比率。结果:proIAPP(1-48)免疫测定法的检测限为0.18 +/- 0.06 pM,与完整的proIAPP(1-67)具有交叉反应性
Context: Islet amyloid is a feature of beta-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 beta cells by processing of its precursor, proIAPP(1-67), via an intermediate form, proIAPP(1-48). Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in beta-cell prohormone processing.Objective: Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes.Design, Setting, and Patients: We developed an immunoassay to detect proIAPP(1-48) in human plasma, and we determined the ratio of proIAPP(1-48) to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls.Results: The proIAPP(1-48) immunoassay had a limit of detection of 0.18 +/- 0.06 pM and cross-reactivity with intact proIAPP(1-67)