Chemical chaperone TUDCA rescues Insulin-mediated vascular relaxation via ER stress inhibition in diabetic rat model

BACKGROUND: Tauroursodeoxycholic acid (TUDCA) has been shown to improve endothelial dysfunction in type 2 diabetes mellitus (T2DM). However, its role in attenuating endothelial insulin resistance in diabetes is not well understood. OBJECTIVES: This study aimed to investigate TUDCA's potential therapeutic effect on endothelial insulin resistance and its underlying mechanisms. METHODS: = 9). Diabetes was induced using a high-fat diet and low-dose streptozotocin. TUDCA (150 mg/kg) was administered to the DMT group during the last two weeks of a 15-week study. Aortic tissues were analyzed for insulin-mediated relaxation, endoplasmic reticulum (ER) stress markers [inositol-requiring kinase 1 (IRE-1), protein kinase-like ER kinase (PERK), and binding immunoglobulin protein (BIP)], end othelial function markers [endothelial nitric oxide synthase (eNOS), protein kinase B (Akt), and insulinreceptor substrate-1 (IRS-1)], oxidative stress [superoxide dismutase activity (SOD) and malondialdehyde level (MDA)] and inflammation [tumor necrosis factor-alpha (TNF-a)] markers. RESULTS: Insulin-mediated relaxation was impaired in diabetic rats (-56.7%) compared to controls (0%), accompanied by elevated ER stress markers and reduced eNOS, Akt, and IRS-1 expression. TUDCA treatment improved relaxation responses (-6.2%) significantly reduced ER stress markers and restored the expression of endothelial markers.