ABSTRACT
The aim of present study is to examine the effect of glucagon-like peptide-1(GLP-1) on diabetes-induced liver injury and explore detailed mechanisms of GLP-1 hepatoprotective effect. 150 male Sprague-Dawley rats were randomly assigned into three groups with equal number, including Sham group, diabetes group and GLP-1 intervention group. Diabetes rat model was performed with intraperitoneal injection of streptozotocin (STZ, 65mg/kg). Fasting blood-glucose of rat model was assessed at 72h after STZ injection to verify diabetes rat model. Rats in Sham group were normally fed. Rats in GLP-1 intervention group received 2 ng/kg GLP-1 intervention, at 2, 4, 6 and 8 weeks after intervention, TUNEL staining were performed to examine apoptosis of liver tissue. PCR and Western blot were performed to examine insulin, GLP-1R, autophagy-associated gene and HDAC-1. Compared with diabetes group, insulin expression of GLP-1 intervention group increased significantly (P<0.05). TUNEL staining at different time showed apoptosis levels of liver tissues were reduced gradually after GLP-1 intervention (P<0.05). Compared with diabetes groups, the expressions of BCL2 and GLP-1R were increased, while the levels of caspase3 and LC3 were reduced in GLP-1 intervention group (P<0.05). GLP-1 treatment decreased levels of phosphorylated AKT, phosphorylated ERK1/2, and HDAC6 in liver tissues (P<0.05). GLP-1 treatment alleviated diabetes-induced liver injury via regulating autophagy. The mechanism of GLP-1 hepatoprotective effect could be via GLP-1R-ERK1/2-HDAC6 signaling pathway.
Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Glucagon-Like Peptide 1/pharmacology , Liver/drug effects , Animals , Apoptosis/drug effects , Autophagy/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/physiopathology , Glucagon-Like Peptide-1 Receptor/metabolism , Histone Deacetylase 6/metabolism , Insulin/metabolism , Liver/metabolism , Liver/physiopathology , MAP Kinase Signaling System/drug effects , Male , Rats, Sprague-Dawley , StreptozocinABSTRACT
Intestinal ischemia reperfusion (IR) causes injury of distant critical organs. Remote intestinal ischemic preconditioning (IP) may confer the cytoprotection in critical organs including lung. The authors hypothesized that intestinal IP would be a prophylactic factor in the prevention of distant lung injury induced by IR. Rats were randomly divided into IR, IP, and Sham (S) group. Compared with IR group in the serum and lung tissue, MPO, MDA, TNF-α, and IL-1 levels were significantly decreased in the IP group. Following the same pattern, NO level in the serum and lung tissue was significantly increased in the IP group. And intestinal IP markedly abolished lung injury scores in contrast to IR group. Moreover, intestinal IP significantly attenuated caspase-3 expression, leading to the low expression of Bax and the high expression of Bcl-2. The present study showed that intestinal IP ameliorates the capacity of anti-oxygen free radical, inhibits the release of pro-inflammatory cytokines and alleviates apoptosis in IR-induced lung injury in rats. Intestinal IP may provide a novel prophylactic strategy for treatment of IR-induced lung injury.
