Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes

Arianne Aslamy, Eunjin Oh, Miwon Ahn, Abu Saleh Md Moin, Mariann Chang, Molly Duncan, Jeannette Hacker-Stratton, Mohamed El-Shahawy, Fouad Kandeel, Linda DiMeglio, Debbie C. Thurmond

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Abstract

Context: Efforts to preserve β-cell mass in the preclinical stages of type 1 diabetes (T1D) are limited by few blood-derived biomarkers of β-cell destruction. Objective: Platelets are proposed sources of blood-derived biomarkers for a variety of diseases, and they show distinct proteomic changes in T1D. Thus, we investigated changes in the exocytosis protein, double C2 domain protein-β (DOC2B) in platelets and islets from T1D humans, and prediabetic nonobese diabetic (NOD) mice. Design, Patients, and Main Outcome Measure: Protein levels of DOC2B were assessed in platelets and islets from prediabeticNODmice and humans, with and without T1D. Seventeen new-onset T1D human subjects (10.3 ± 3.8 years) were recruited immediately following diagnosis, and platelet DOC2B levels were compared with 14 matched nondiabetic subjects (11.4 ± 2.9 years). Furthermore, DOC2B levels were assessed in T1D human pancreatic tissue samples, cytokine-stimulated human islets ex vivo, and platelets from T1D subjects before and after islet transplantation. Results: DOC2B protein abundancewas substantially reduced in prediabeticNODmouse platelets, and these changes were mirrored in the pancreatic islets from the same mice. Likewise, human DOC2B levels were reduced over twofold in platelets fromnew-onset T1D human subjects, and this reduction wasmirrored in T1D human islets. Cytokine stimulation of normal islets reduced DOC2B expression ex vivo. Remarkably, platelet DOC2B levels increased after islet transplantation in patients with T1D. Conclusions: Reduction of DOC2B is an early feature of T1D, and DOC2B abundance may serve as a valuable in vivo indicator of β-cell mass and an early biomarker of T1D.

Original languageEnglish (US)
Pages (from-to)1966-1976
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number5
DOIs
StatePublished - May 1 2018

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Aslamy, A., Oh, E., Ahn, M., Moin, A. S. M., Chang, M., Duncan, M., Hacker-Stratton, J., El-Shahawy, M., Kandeel, F., DiMeglio, L., & Thurmond, D. C. (2018). Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes. Journal of Clinical Endocrinology and Metabolism, 103(5), 1966-1976. https://doi.org/10.1210/jc.2017-02492