Association between O-GlcNAc levels and platelet function in obese insulin-resistant subjects

• Published in: Glycoconjugate journal Vol. 41; no. 4-5; pp. 291 - 300
• Main Authors: Hernández-Huerta, María Teresa, Martínez-Cruz, Ruth, Pérez-Campos Mayoral, Laura, Pina-Canseco, María del Socorro, Solórzano-Mata, Carlos Josué, Martínez-Cruz, Margarito, Vásquez Martínez, Itzel Patricia, Zenteno, Edgar, Laguna Barrios, Luis Ángel, Matias-Cervantes, Carlos Alberto, Pérez-Campos Mayoral, Eduardo, Pérez-Campos, Eduardo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2024; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Body mass index; Calcium (intracellular); Diabetes mellitus (non-insulin dependent); Flow cytometry; Glucosamine; Hyperactivity; Immunofluorescence; Insulin resistance; Integrins; Intracellular; Life Sciences; N-Acetylglucosamine; O-GlcNAcylation; Obesity; P-selectin; PAC1 protein; Pathology; Platelet aggregation; Thrombin; Platelet hyperactivity; Glucose metabolism; Obese insulin-resistant; Intracellular calcium; Pathways; Hemostasis disturbances; O-GlcNAc
• ISSN: 0282-0080; 1573-4986; 1573-4986
• DOI: 10.1007/s10719-024-10164-9

Obesity is an epidemic associated with platelet and vascular disorders. Platelet O-GlcNAcylation has been poorly studied in obese subjects. We aimed to evaluate O-linked N-acetyl-glucosamine (O-GlcNAc) levels and platelet activity in obese insulin-resistant (ObIR) subjects. Six healthy and six insulin-resistant obese subjects with a body mass index of 22.6 kg/m 2 (SD ± 2.2) and 35.6 kg/m 2 (SD ± 3.8), respectively, were included. Flow cytometry was used to measure markers of platelet activity, expression of P-selectin (CD62P antibody), glycoprotein IIb/IIIa (integrins αIIbβ3 binding to PAC-1 antibody), and thrombin stimulation. O-GlcNAc was determined in the platelets of all test subjects by cytofluometry, intracellular calcium, percentage of platelet aggregation, and immunofluorescence microscopy and Western blot were used to assess O-GlcNAc and OGT (O-GlcNAc transferase) in platelets. Platelets from ObIR subjects had on average 221.4 nM intracellular calcium, 81.89% PAC-1, 22.85% CD62P, 57.48% OGT, and 66.62% O-GlcNAc, while platelets from healthy subjects had on average 719.2 nM intracellular calcium, 4.99% PAC-1, 3.17% CD62P, 18.38% OGT, and 23.41% O-GlcNAc. ObIR subjects showed lower platelet aggregation than healthy subjects, 13.83% and 54%, respectively. The results show that ObIR subjects have increased O-GlcNAc, and increased intraplatelet calcium associated with platelet hyperactivity and compared to healthy subjects, suggesting that changes in platelet protein O-GlcNAcylation and platelet activity might serve as a possible prognostic tool for insulin resistance, prediabetes and its progression to type 2 diabetes mellitus.