Exploring the Role of Osteoglycin in Type 2 Diabetes: Implications for Insulin Resistance and Vascular Pathophysiology

  1. González-Salvatierra, Sheila 4
  2. García-Fontana, Beatriz 5
  3. Martínez-Heredia, Luis 3
  4. Lacal, Jesus 1
  5. Andújar-Vera, Francisco 8
  6. Sanabria-de la Torre, Raquel 2
  7. Moratalla-Aranda, Enrique 6
  8. Lozano-Alonso, Silvia 10
  9. García-Fontana, Cristina 9
  10. Muñoz-Torres, Manuel 7
  1. 1 Department of Microbiology and Genetics, University of Salamanca (USAL), Institute of Biomedical Research of Salamanca, Spain
  2. 2 Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Biosanitary Research Institute of Granada, Spain
  3. 3 Biosanitary Research Institute of Granada, Biosanitary Research Institute of Granada, Spain
  4. 4 Department of Biochemistry and Molecular Biology II, University of Granada, Biosanitary Research Institute of Granada, Granada, Spain
  5. 5 Department of Biochemistry and Molecular Biology II, University of Granada, Instituto de Salud Carlos III, Granada, Spain
  6. 6 Nuclear Medicine Unit, Hospital Universitario Clínico San Cecilio, Biosanitary Research Institute of Granada, Spain
  7. 7 Endocrinology and Nutrition Service, University Hospital San Cecilio, Granada, Spain
  8. 8 Department of Computer Science and Artificial Intelligence, University of Granada, Andalusian Research Institute in Data Science and Computational Intelligence, Spain
  9. 9 Endocrinology and Nutrition Unit, Hospital Universitario Clínico San Cecilio, Biosanitary Research Institute of Granada, Spain
  10. 10 Angiology and Vascular Surgery Unit, Hospital Universitario Clínico San Cecilio, 18016 Granada, Spain., Biosanitary Research Institute of Granada, Spain
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Revista:
American Journal of Physiology-Endocrinology and Metabolism

ISSN: 0193-1849,  1522-1555

Año de publicación: 2023

Volumen: 325

Número: 4

Tipo: Artículo

DOI: 10.1152/AJPENDO.00320.2023 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: American Journal of Physiology-Endocrinology and Metabolism

Resumen

Osteoglycin, a fundamental proteoglycan within the vascular extracellular matrix, is expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with cardiovascular disease (CVD) but the role of osteoglycin in the development of CVD is controversial to date. Therefore, our aims are to determine and compare the level of osteoglycin in T2D patients with/without CVD versus control subjects both at serum and vascular tissue, and to analyze in vitro the role of osteoglycin in VSMCs under calcified conditions. For this, serum osteoglycin levels were determined by ELISA in 117 controls and 129 T2D patients (46 with CVD and 83 without CVD), revealing a significant increase in T2D patients compared to controls. Osteoglycin level was not estimator of CVD but correlated with markers of insulin resistance (triglycerides and triglycerides/ high-density lipoprotein cholesterol index) in T2D patients. At the vascular level, osteoglycin expression was assessed by RT-qPCR and immunohistochemistry, and no significant differences were observed between calcified arteries from T2D patients and non-calcified arteries from controls. In vitro experiments using VSMCs (mock and overexpressing osteoglycin) under calcifying conditions were performed to analyze the osteoglycin function. The overexpression of osteoglycin in VMSCs under calcifying conditions revealed an increase of cell proliferation without effect on apoptosis, and an up-regulation of the expression of autotaxin (ATX) involved in inflammatory processes. In conclusion, osteoglycin could play a role in glycemic homeostasis, being a potential biomarker of insulin resistance in T2D patients. Furthermore, osteoglycin could indirectly participate in the development of atherosclerosis through its regulatory effect on ATX and by proliferating VSMCs.

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