The Serum and Saliva Proteome of Dogs with Diabetes Mellitus

SIMPLE SUMMARY: The present study describes for the first time the differences in the serum and saliva proteomes between healthy dogs and dogs with diabetes mellitus by a high- throughput proteomic approach. More than 1000 proteins were identified, and 16 proteins in serum and 26 in saliva showed significant changes between both groups. Additionally, pathways that showed changes were discussed in order to improve the understanding of the pathophysiology of the disease and one protein in serum (haptoglobin) was successfully verified. The results of the present study could be a source of potential biomarkers for canine diabetes mellitus in saliva and serum and also contribute to increase the knowledge of the pathophysiology of the disease. ABSTRACT: This study aims to evaluate the changes in salivary and serum proteomes that occur in canine diabetes mellitus type-1 (DM) through a high-throughput quantitative proteomic analysis. The proteomes of 10 paired serum and saliva samples from healthy controls (HC group, n = 5) and dogs with untreated DM (DM group, n = 5) were analyzed using Tandem Mass Tags (TMT)-based proteomic approach. Additionally, 24 serum samples from healthy controls and untreated DM were used to validate haptoglobin in serum. The TMT analysis quantified 767 and 389 proteins in saliva and serum, respectively. Of those, 16 unique proteins in serum and 26 in saliva were differently represented between DM and HC groups. The verification of haptoglobin in serum was in concordance with the proteomic data. Our results pointed out changes in both saliva and serum proteomes that reflect different physiopathological changes in dogs with DM. Although some of the proteins identified here, such as malate dehydrogenase or glyceraldehyde-3-phosphate dehydrogenase, were previously related with DM in dogs, most of the proteins modulated in serum and saliva are described in canine DM for the first time and could be a source of potential biomarkers of the disease. Additionally, the molecular function, biological process, pathways and protein class of the differential proteins were revealed, which could improve the understanding of the disease’s pathological mechanisms.