Identification of Hybrid Insulin Peptides (HIPs) in Mouse and Human Islets by Mass Spectrometry

We recently discovered hybrid insulin peptides (HIPs) as a novel class of post-translationally modified peptides in murine-derived beta cell tumors, and we demonstrated that these molecules are autoantigens in type 1 diabetes (T1D). A HIP consists of an insulin fragment linked to another secretory g...

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Bibliographic Details
Published in:	Journal of proteome research 2019-03, Vol.18 (3), p.814-825
Main Authors:	Aaron Wiles, T, Powell, Roger, Michel, Cole Robert, Scott Beard, K, Hohenstein, Anita, Bradley, Brenda, Reisdorph, Nichole, Haskins, Kathryn, Delong, Thomas
Format:	Article
Language:	eng
Subjects:	Animals Autoantigens - analysis Autoantigens - blood Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - metabolism Humans Insulin - chemistry Islets of Langerhans - chemistry Mass Spectrometry - methods Mice Peptides - analysis Peptides - chemistry
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Summary:	We recently discovered hybrid insulin peptides (HIPs) as a novel class of post-translationally modified peptides in murine-derived beta cell tumors, and we demonstrated that these molecules are autoantigens in type 1 diabetes (T1D). A HIP consists of an insulin fragment linked to another secretory granule peptide via a peptide bond. We verified that autoreactive CD4 T cells in both mouse and human autoimmune diabetes recognize these modified peptides. Here, we use mass spectrometric analyses to confirm the presence of HIPs in both mouse and human pancreatic islets. We also present criteria for the confident identification of these peptides. This work supports the hypothesis that HIPs are autoantigens in human T1D and provides a foundation for future efforts to interrogate this previously unknown component of the beta cell proteome.
ISSN:	1535-3893 1535-3907