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.

J Clin Endocrinol Metab. 2017 Mar 24;:

Authors: Courtade JA, Klimek-Abercrombie AM, Chen YC, Patel N, Lu PY, Speake C, Orban PC, Najafian B, Meneilly G, Greenbaum CJ, Warnock GL, Panagiotopoulos C, Verchere CB

Abstract
Context: Islet amyloid is a feature of beta cell failure in type 2 diabetes (T2D) and type 1 diabetic (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, proIAPP1-67, via an intermediate form, proIAPP1-48. 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 proIAPP1-48 in human plasma, and determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls.
Results: The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 less than 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.
Conclusion: Beta 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 beta cell stress and dysfunction.

PMID: 28368485 [PubMed - as supplied by publisher]

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