Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes.

Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes.

J Clin Endocrinol Metab. 2018 Mar 01;:

Authors: Aslamy A, Oh E, Ahn M, Moin ASM, Chang M, Duncan M, Hacker-Stratton J, El-Shahawy M, Kandeel F, DiMeglio LA, Thurmond DC

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 pre-diabetic NOD mice.
Design, Patients, and Main Outcome Measure: Protein levels of DOC2B were assessed in platelets and islets from pre-diabetic NOD mice 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 to 14 matched non-diabetic subjects (11.4 ± 2.9 years). Also, 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 abundance was substantially reduced in prediabetic NOD mouse platelets, and these changes were mirrored in the pancreatic islets from the same mice. Similarly, human DOC2B levels were reduced over 2-fold in platelets from new-onset T1D human subjects, and this reduction was mirrored in T1D human islets. Cytokine stimulation of normal islets reduced DOC2B expression ex vivo. Remarkably, platelet DOC2B levels increased after islet transplantation in T1D patients.
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 early biomarker of T1D.

PMID: 29506054 [PubMed - as supplied by publisher]

http://ift.tt/2G2gwud