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- Title
Potential of Protein Phosphatase Inhibitor 1 As Biomarker of Pancreatic β-Cell Injury In Vitro and In Vivo.
- Authors
Lei Jiang; Brackeva, Benedicte; Zhidong Ling; Kramer, Gertjan; Aerts, Johannes M.; Schuit, Frans; Keymeulen, Bart; Pipeleers, Daniel; Gorus, Frans; Martens, Geert A.
- Abstract
There is a need for plasma-based tests that can directly measure the extent of β-cell injury in vivo in patients receiving islet grafts and in animal models. In this study, we propose protein phosphatase 1, regulatory (inhibitor) subunit 1A (PPP1R1A) as a novel biomarker for acute β-cell destruction. Liquid chromatographytandem mass spectrometry proteome analysis of fluorescence-activated cell sorter-purified β-cells, tissue-comparative Western blotting, and immunohistochemistry indicated relatively high molar abundance and selectivity of PPP1R1A in β-cells. PPP1R1A was discharged into the extracelhilar space of chemically injured rat and human islets in vitro, proportionate to the extent of β-cell death. Streptozotocin injection in rats led to a progressive PPP1R1A depletion from the cytoplasm of disintegrating β-cells and a marked surge in plasma levels detectable by an affinity-capture method. A similar massive PPP1R1A discharge in blood was also detected in three patients immediately after intraportal islet transplantation. Our findings provide first proof-of-principle for PPP1R1A as real-time biomarker of β-cell destruction in an mal models and patients and warrant development of more sensitive methods for its further validation in clinical trials.
- Publication
Diabetes, 2013, Vol 62, Issue 8, p2683
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db12-1507