Increased Insulin Resistance by Dextran Sulfate Sodium is Associated with Increased D‐Amino Acids and Lipopolysaccharides in Rat

Abstract

Dextran sulfate sodium (DSS) is known to increase intestinal permeability. Recently we observed that DSS enhanced insulin resistance (IR) in rat. We hypothesize that DSS increases hepatic exposure of bacterial components such as lipopolysaccharides (LPS) and D-amino acids (DAA), which in turn affect liver metabolism. LPS is the major component of the outer membrane of Gram-negative bacteria. DAA are major components of bacterial cell wall peptidoglycan. In liver, DAA is oxidized by DAA specific oxidase (DAO) and generate hydrogen peroxide. This study investigates how DSS affects liver metabolism. Sprague Dawley rats were divided into 2 groups and treated with or without DSS for 16 weeks. Portal and peripheral blood were collected when animals were sacrificed. LPS levels were measured using a chromogenic assay kit. DAA assay was established using a DAO based method. For the first time, we have established a convenient method to measure serum DAA concentrations with a sensitivity of 2 µM. DAA concentrations in portal blood were significantly correlated with that in peripheral blood (R=0.7, p<0.01), which indicates that measuring DAA levels in peripheral blood is useful to reflect its levels in portal blood because practically it is not very easy to obtain portal blood. Compared to control group, DSS increased DAA concentrations in portal and peripheral serum (DSS/control: portal, 1.2, p<0.05; peripheral, 1.5, p<0.05). DSS also increased LPS concentrations (DSS/control: 1.6, p<0.05) in portal serum. These results suggest that increased DAA and LPS levels may contribute to DSS-enhanced IR.