Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats

Abstract

Adiponectin can improve both glucose metabolism and insulin resistance via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Activated AMPK phosphorylates a variety of intracellular proteins, including acetyl coenzyme A carboxylase (ACC) that is involved in fatty acid oxidation. Adenosine monophosphate-activated protein kinase increases glucose transport by stimulating the translocation of glucose transporter 4 (GLUT4) to the sarcolemma in the heart. Adiponectin exerts its effect through adiponectin receptors, which are predominantly expressed in the liver and skeletal muscle. It is unknown whether the cardiac expression of adiponectin and its receptors is changed in diabetic rats. In the present study, we investigated the protein expression of adiponectin and its receptors in streptozotocin (STZ)-induced diabetic rat hearts. We also explored whether the levels of AMPK, ACC, and GLUT4 will be altered with the changed adiponectin and its receptors in STZ diabetic rat hearts. Plasma and cardiac adiponectin levels were measured by radioimmunoassay. Plasma and cardiac interleukin 6 and plasma tumor necrosis factor α (TNF-α) were assayed by enzyme-linked immunosorbent assay. Cardiac adiponectin receptors, AMPK-α, ACC, GLUT4, and TNF-α were analyzed by Western blot in control and STZ diabetic rats. The plasma adiponectin level was decreased, but the cardiac protein expression of adiponectin receptor 1 was increased in diabetic rats. There was no difference in the cardiac adiponectin level and the cardiac adiponectin receptor 2 protein expression between control and diabetic rats. The phosphorylation of AMPK-α and protein expression of GLUT4 were decreased, but the phosphorylation of ACC was unchanged in diabetic rat hearts. Plasma and cardiac levels of interleukin 6 and TNF-α were increased in diabetic rats. In conclusion, STZ-induced diabetes up-regulates adiponectin receptors in the heart. Despite an increase in cardiac adiponectin receptor 1 expression, there is an increased cardiac inflammatory response and a decreased GLUT4 protein expression associated with a reduction in circulating adiponectin. © 2007 Elsevier Inc. All rights reserved.