Evaluation of coronary function in female rats with severe type 1 diabetes: Effects of combined treatment with insulin and pyridoxamine

Author(s)

Sousa, Andressa S. ; Passos, Matheus P. ; Ruberti, Olivia M. ; Jarrete, Aline P. ; Delbin, Maria A.

• Document type: Journal article
• Source: MICROVASCULAR RESEARCH; v. 146, p. 10-pg., 2023-01-05.

Abstract

Background: This study aimed to evaluate the coronary function, myocardium, and epicardial adipose tissue (EAT) in female rats with severe type 1 diabetes and the effects of combined treatment with insulin and pyri-doxamine (AGEs inhibitor).Methods: Female Wistar rats were divided into groups: control (CTR, n = 13), type 1 diabetes (DM1, n = 12), type 1 diabetes treated with insulin (DM1 + INS, n = 11), and type 1 diabetes treated with insulin and pyridoxamine (DM1 + INS + PDX, n = 14). The vascular responsiveness was performed in the septal coronary artery and the protein expressions of AGE, RAGE, GPER, NF-kB was evaluated in the left ventricle (LV), as well as the reactive oxygen species (ROS) was measured in LV and in EAT. We analyzed plasma levels of glucose, estradiol, N epsilon-carboxymethylisine (CML), thiobarbituric acid reactive substances (TBARS), catalase (CAT), and superoxide dismutase (SOD).Results: The maximal responses to ACh were reduced in the DM1 compared with the CTR group, accompanied by an increase in circulating glucose, CML, and TBARS. Additionally, the expression of NF-kB in LV and generation of ROS in the presence of MnTMPyP (SOD mimetic) were increased in the DM1 group compared with CTR. Only the combined treatment was effective for fully re-establish ACh relaxation response, NF-kB protein expression, ROS generation, and increased SOD activity in the DM1 + INS + PDX group.Conclusion: The reduction of the endothelium-dependent relaxation response in the septal coronary artery of female rats with severe type 1 diabetes was normalized with the combined treatment with insulin and pyri-doxamine, associated with reduced inflammation and oxidative stress in the myocardium and increased circu-lating antioxidant activity. (AU)

• FAPESP's process: 16/16351-5 - Coronary function in type 1 diabetic female rats: the effects of treatment with inhibitors of advanced glycation end-products (ages) and protein kinase c beta (PKC-beta)
• Grantee: Maria Andréia Delbin
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/22670-9 - Cardiac effects of advanced glycation end products inhibitor (pyridoxamine) in type 1 diabetic female rats
• Grantee: Matheus Pena Passos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation