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Objective To investigate the potential value of annexin A1 (ANXA1) in preventing and alleviating microvascular complications in type 1 diabetes (T1D). Methods Plasma ANXA1 level was detected in T1D patients and healthy people. T1D mice were treated with human recombinant ANXA1 (rANXA1) for 8 weeks. After the administration, the mice were subjected to the oral glucose tolerance test (OGTT). The left ventricular ejection fraction (EF) and left ventricular fraction shortening (FS) of the mice were evaluated by echocardiography. Serum urea and creatinine of mice in each group were detected by Au400. The concentration of insulin, urinary albumin and ANXA1 were measured by ELISA. The heart and kidney tissues of mice were stained with PAS or Sirius red. Western blot was used to detect protein kinase B (Akt)/p-Akt, p38/p-p38, c-Jun amino terminal kinase (JNK)/p-JNK, and extracellular signal-regulated kinase (ERK1/2)/p-ERK1/2 expression level. Results Comparing with healthy people, the plasma ANXA1 level of T1D patients decreased, while the level of C-reactive protein (CRP) increased (P＜0.05). hrANXA1 reduced the area under the curve (AUC) of the T1D mouse glucose tolerance test (OGTT) and increased serum insulin level(P＜0.05). hrANXA1 increased the left ventricular ejection fraction (EF) and left ventricular short axis shortening rate (FS) of mice (P＜0.05); hrANXA1 reduced the serum urinary albumin to creatinine ratio (ACR) and urea level of mice (P＜0.05). hrANXA1 promoted the phosphorylation of Akt in mouse heart and kidney tissues, and inhibited the phosphorylation of p38, JNK and ERK1/2 (P＜0.05). Conclusions The protective effect of ANXA1 on the heart and kidney of T1D mice is attributed to the inhibition of MAPK signaling pathway and activation of Akt survival pathway.