CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma

Claudia Paola Pérez-Macedonio; Eugenia Flores-Alfaro; Luz Del C Alarcón-Romero; Amalia Vences-Velázquez; Natividad Castro-Alarcón; Eduardo Martínez-Martínez; Monica Ramirez

doi:10.7717/peerj.13656

CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma

PeerJ. 2022 Jul 12:10:e13656. doi: 10.7717/peerj.13656. eCollection 2022.

Authors

Claudia Paola Pérez-Macedonio¹, Eugenia Flores-Alfaro¹, Luz Del C Alarcón-Romero¹, Amalia Vences-Velázquez¹, Natividad Castro-Alarcón¹, Eduardo Martínez-Martínez², Monica Ramirez³

Affiliations

¹ Laboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
² Laboratorio del Metabolismo de RNA y Vesículas Extracelulares, Instituto Nacional de Medicina Genómica (INMEGEN), México, México.
³ CONACYT-Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.

Abstract

Background: Exosomes are microvesicles that actively participate in signaling mechanisms and depending on their content can contribute to the development of different pathologies, such as diabetes and cardiovascular disease.

Objective: The aim of this study was to evaluate the association of cystatin C, CD26, and CD14 proteins in serum exosomes from patients with Type 2 Diabetes (T2D), metabolic syndrome (MetS), and atherogenic index of plasma (AIP).

Methods: Serum exosomes were isolated by ultracentrifugation from 147 individuals with and without diabetes. Both anthropometric and metabolic parameters were registered from everyone. The levels of exosomal proteins cystatin C, CD26, and CD14 were quantified by ELISA. The association between protein levels and T2D or atherogenic risk factors was analyzed by linear regression and generalized regression models.

Results: We observed a significant correlation of increased glucose with elevated levels of Cystatin C, and an effect of T2D on the levels of CD26 (β = 45.8 pg/µg; p = 0.001) and CD14 (β = 168 pg/µg; p < 0.001) compared to subjects without T2D. CD14 was significantly related to T2D, metabolic syndrome, glucose, and the Atherogenic Index of Plasma (AIP). Additionally, we observed a significant effect of metabolic syndrome MetS on the increase of exosomal Cystatin C and CD14.

Conclusions: T2D may contribute to the increase of CD14 protein contained in exosomes, as well as to the predisposition of atherogenic events development due to its relationship with the increase in serum triglyceride concentrations and the AIP score. Finally, the increased levels of CD14 and Cystatin C in exosomes are related to MetS. The analysis of exosome contents of diabetic patients remains an incipient field, so extensive characterization is crucial for their use as biomarkers or to analyze their possible contribution to diabetic complications.

Keywords: Atherogenic index of plasma; CD14; CD26; Cystatin c; Diabetes; Exosomes; Metabolic syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis*
Cystatin C
Diabetes Mellitus, Type 2* / complications
Dipeptidyl Peptidase 4
Exosomes* / metabolism
Glucose
Humans
Metabolic Syndrome*

Substances

Cystatin C
Dipeptidyl Peptidase 4
Glucose
CD14 protein, human
CST3 protein, human

Grants and funding

This work was supported by the Fondo Mixto CONACYT-GUE (249719); INMEGEN (21/2015/I), CONACYT-2015 (258589), and the infrastructure grant CONACYT-2016 (269696). During the study, CPPM was a grant recipient of CONACyT-Mexico (705009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.