Effect of CAPE‐pNO2 against type 2 diabetes mellitus via the AMPK/GLUT4/ GSK3&bgr;/PPAR&agr; pathway in HFD/STZ‐induced diabetic mice

Abstract

ABSTRACT CAPE‐pNO2, a para‐nitro derivative of caffeic acid phenethyl ester (CAPE), has been proved to exert stronger effects on diabetic complications in diabetic mice. The present study aimed at probing into the effect and potential mechanism of CAPE‐pNO2 in type 2 diabetes mellitus (T2DM) compared with CAPE on model animal. Diabetic model was established by feeding one month of high‐fat‐diet (HFD) before injection of 40 mg/kg streptozotocin (STZ) for five days, and the normal diet mice were set as control group. Model mice were treated by CAPE‐pNO2 for one month again, the levels of blood glucose, blood lipid and blood insulin significantly decreased. In addition, the myocardial enzymes (creatine Kinase and lactate dehydrogenase) and liver transaminase (aspartate aminotransferase and alanine aminotransferase) activities decreased. Furthermore, CAPE‐pNO2 could alleviate pancreatic damage, myocardial injury and hepatic steatosis caused by diabetes mellitus, and significantly improved the islet mass, &bgr; cell survival and the hepatic glycogen content. Besides, CAPE‐pNO2 enhanced the expression of phosphorylation‐AMP‐activated protein kinas (p‐AMPK) (Thr172), GLUT4, peroxisome proliferator‐activated receptor‐&agr; (PPAR&agr;) and p‐Akt (Ser473), and inhibited the expression of glycogen synthase kinase 3&bgr; (GSK3&bgr;) and p‐JNK (Thr183/Tyr185) in liver. All of those effects are better than CAPE generally. It suggested that CAPE‐pNO2 ameliorated type 2 diabetes mellitus by effectively protecting islet &bgr; cell and improving the insulin resistance via the AMPK/GLUT4/GSK3&bgr;/PPAR&agr; pathway. Graphical abstract Figure. No Caption available.