Relationship between angiotensin 1-7, diabetes and endoplasmic reticulum stress of diabetic kidney

Abstract

Objective To investigate the level of angiotensin 1-7(Ang1-7) in patients with diabetes, and to study the effects of Ang1-7 on endoplasmic reticulum (ER) stress in the kidney of diabetic rats. Methods Ninety-five subjects without diagnosed diabetes were screened in Tianjin Seaside People′s Hospital from December 2014 to June 2015. Oral glucose tolerance test was implemented. According to the level of blood glucose, subjects were divided into three groups: healthy group (n=31), impaired glucose group (n=32), and diabetes group (n=32). Body weight, waist circumference, blood pressure, liver function, renal function, Ang1-7, angiotensin-converting enzyme(ACE)2 and other indicators were detected. Relationship between blood glucose and Ang1-7 and ACE2 were analyzed. In addition, ten healthy male Sprague-Dawley (SD) rats (150-200 g) were chosen to induce diabetes through intraperitoneal injection of streptozotocin, and all succeeded. Ten diabetic rats were randomly divided into Ang1-7 group and diabetes group according to the random number method, and pumped into Ang1-7 or saline solution, respectively, with five rats in each group. Other five healthy SD rats were chosen as normal group. All rats were sacrificed after intervention for two weeks. Kidney specimens were used to test the level of ER stress proteins, including glucose-regulated protein(GRP)78, activity of transcription factor (ATF)4, enhancer binding protein homologous protein (CHOP), by Western Blotting and Real-time Quantitative PCR. Results Compared with healthy group, levels of triglycerides, ACE2, Ang1-7 in impaired glucose group and diabetes group were increased, especially the diabetes group(F=5.57, 6.12, 5.44, all P<0.01). Pearson correlation analysis showed that fasting blood glucose and postprandial blood glucose in diabetes group and impaired glucose group were positive correlated with Ang1-7(r=0.69, 0.45, all P<0.01; r=0.54, 0.52, all P<0.01). Compared with normal group, levels of GRP78, ATF4, and CHOP were increased significantly in diabetes group; compared with diabetes group, levels of GRP78, ATF4, and CHOP were significantly reduced in Ang1-7 group(t=20.3, 25.7, 19.6, all P<0.05). Compared with normal group, mRNA levels of GRP78, ATF4, and CHOP were increased significantly in diabetes group; compared with diabetes group, levels of GRP78, ATF4, and CHOP were significantly reduced in Ang1-7 group (t=15.1, 11.6, 12.3, all P<0.05). Conclusions The level of Ang1-7 evelates with the increase of blood glucose concentration in subjects. Ang1-7 reduces ER stress in the kidney of diabetic rats. Key words: Angiotensin 1-7; Diabetes mellitus; Diabetic kidney disease; Endoplasmic reticulum stress