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

作者：Courtade Jaques A; Klimek Abercrombie Agnieszka M; Chen Yi Chun; Patel Nirja; Lu Phoebe Y T; Speake Cate; Orban Paul C; Najafian Behzad; Meneilly Graydon; Greenbaum Carla J; Warnock Garth L; Panagiotopoulos Constadina; Verchere C Bruce^*

来源：Journal of Clinical Endocrinology & Metabolism, 2017, 102(7): 2595-2603.

DOI：10.1210/jc.2016-2773

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) <15%. Healthy individuals had plasma concentrations of proIAPP(1-48) immunoreactivity of 1.5 +/- 0.2 pM and a proIAPP(1-48) to total IAPP ratio of 0.28 +/- 0.03. Plasma concentrations of proIAPP(1-48) 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.
Conclusion: The beta cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP(1-48)-to-IAPP immunoreactivity may have value as a biomarker of beta-cell stress and dysfunction.

• 出版日期2017-7