The imidazoline I₂receptor agonist 2-BFI attenuates Glucolipotoxicity in cardiomyocytes

Cardiovascular complications are the leading cause of mortality in diabetic patients. Although oxidative stress has been identified as a major cause of cardiac injury in diabetic patients, clinical trials regarding antioxidant therapy have shown limited benefits on cardiovascular outcomes, indicating the need to continue investigating the mechanisms behind diabetic cardiac injury. A potential cause of diabetic cardiac injury is increased lysosomal membrane permeability (LMP), where stressors such as hyperglycemia and hyperlipidemia have been shown to rupture the membrane, leading to lysosomal cell death. 2-BFI, an imidazoline I 2 receptor agonist, has been shown to stabilize lysosomes and prevent oxidative stress in cytotoxicity. Our aim for this study is to determine whether 2-BFI can prevent LMP, thereby reducing diabetic cardiomyocyte death. H9C2 cardiomyoblasts were cultured with different amounts of glucose and/or palmitic acid (PA) in the following four groups: 1) 5.5 mM glucose (normal glucose, NG); 2) 35 mM glucose (high glucose, HG); 3) NG + 50 μM PA; and 4) HG + PA. The cells were cultured with or without 2-BFI. The dual fluorescence imaging-based LMP reporter (Galectin3-mRFP-EGFP) assay showed that HG + PA induces LMP in cardiomyocytes. The cardiomyocyte death was measured utilizing Propidium Iodide staining and protein levels of cell death marker proteins. The results showed that HG and PA induced cell death, which was attenuated by 2-BFI Further research will be warranted to determine whether 2BFI improves glucolipotoxicity-induced LMP in cardiomyocytes. This study was supported by NIH grants 1R15HL163707-01A1 (QL), 1R15HL161737-01 (SK) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.