Hepatic modulation of glucose metabolism by kinin in experimental diabetes

Abstract

Kinins are peptides formed by 8-11 amino acids, such as bradykinin, kallidin and their metabolites. It has biological action through the binding to membrane receptors B1 and B2. It has indirect vasodilator action, because stimulates the nitric oxide release and is related to inflammatory conditions. In the arterial system, bradykinin has a hypotensive action, whereas in the portal system it has hypertensive action mediated by B2 receptors (via nitric oxide). It was verified experimentally that during the process of hepatic cirrhosis and hepatectomy, there is an increase of B1 receptor expression, suggesting some role of this receptor in the fibrogenesis as well as the cellular remodeling that occurs in these situations. In a pathological process such as diabetes, there has been an increase in B1 receptor signalling in different tissues, mainly the central nervous system, suggesting that hyperglycemia is a stimulus for the kallikrein-kinin system. We have recently verified that portal hypertensive response to BK is maintained in DM1 and DM2 animals. However, in the fasted state there is lower portal hypertensive response to BK in DM1 animals. In addition, kinins are related to glucose metabolism inhibiting gluconeogenesis in fasting. Thus, this project aims to study the expression or not of enzymes related to the metabolism of glucose in liver of animals submitted to experimental model of Diabetes. (AU)