2021/12/01 by Di Zhu, Xiaotian Zhang, Fenglin Wang +3
Medicine · #Adipokines, Inflammation, and Metabolic Diseases #Adipose Tissue and Metabolism #Sirtuins and Resveratrol in Medicine
paper · pdf · doi:10.1016/j.diabres.2021.109170
openalex publication_date 2021/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
AIMS: Cardiac microvascular dysfunction is a common feature across cardiovascular complications in diabetes, while effective therapy remains elusive. This study was designed to evaluate the effect of irisin on cardiac microvascular injury in type 2 diabetes mellitus (T2DM). METHODS: T2DM was induced in C57BL/6J mice. A cohort diabetic mice received a 12-week treatment of irisin. Cardiac function and microvessel density were evaluated. Whether irisin directly regulates cardiac microvascular endothelial cells (CMECs) function was determined in vitro. Discovery-drive approaches followed by cause-effect analysis were used to uncover the molecular mechanisms. RESULTS: Irisin improved cardiac function in diabetic mice, and increased microvessel density. In vitro study revealed that irisin promoted CMECs proliferation and reduced high glucose and high lipid (HGHL)-induced apoptosis. Mechanistically, irisin increased mRNA and protein levels of heme oxygenase 1 (HO-1), superoxide dismutase 1 and superoxide dismutase 2, among which HO-1 ranked top. Irisin stimulated the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and nuclear factor erythroid-derived 2-like 2 (Nrf2) nuclear translocation, while U0126 (the inhibitor of ERK1/2) inhibited irisin-induced Nrf2 nuclear translocation and HO-1 expression. Nrf2 siRNA inhibited irisin's antioxidative effects. CONCLUSION: Irisin could rescue cardiac microvessels against oxidative stress and apoptosis in diabetes via ERK1/2/Nrf2/HO-1 pathway.