Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Study on the protective mechanism of dexmedetomidine on the liver of perioperative diabetic patients: A randomized controlled trial.

BACKGROUND: Although several studies have reported that dexmedetomidine is a highly selective α2-adrenergic receptor agonist that protects liver function in perioperative patients by inhibiting oxidative stress (OS) and inflammatory response, patients with type 2 diabetes mellitus (T2DM) have not been included in the previous studies. The purpose of this study was to investigate the effects of perioperative low-dose dexmedetomidine on perioperative liver function in T2DM patients. METHODS: This was a single-center, placebo-controlled randomized trial. Fifty-four T2DM patients scheduled for debridement of lower extremity ulcers were included in this study and randomly divided into 2 groups (n = 27 per group): the dexmedetomidine group (DEX group) and the control group (CON group). Continuous intravenous infusion of dexmedetomidine (DEX group) or normal saline (CON group) was administered from the completion of monitoring to the end of surgery. All participants received femoral and sciatic nerve block with 0.33% ropivacaine. The main result was the activity of liver enzymes (AST, ALT) reflecting liver function. The secondary results included variables reflecting blood glucose (Glu), blood lipids (TG, HDL, LDL, total cholesterol), biomarkers of OS (MDA, SOD), and systemic inflammatory response (TNF-α, IL-6). RESULTS: Compared with CON group, DEX group exhibited a reduction in hemodynamic parameters, Glu, systemic inflammatory response, and liver injury indicators. OS response MDA activity was lower in DEX group than in CON group, while SOD was higher than that in CON group. The variables reflecting lipid metabolism function showed no differences between the groups. CONCLUSION SUBSECTIONS: Dexmedetomidine administered perioperatively can reduce Glu levels and protect the liver by attenuating OS injury and inflammatory response in T2DM patients without any potential risk.