Increasing intestinal reactive oxygen species reverses diabetes-induced inflammation (MUC2P.928)

Abstract

Abstract Systemic inflammation appears to persist in diabetic patient. To examine the role of reactive oxygen species (ROS) of intestine in DM-induced inflammation, streptozotocin (STZ)-induced diabetes and Ins2Akita (Ins2Akita mutation mutant) mice were used. STZ mice demonstrated a significant decrease of Lacobacilli as well as ROS production and a marked increase of p-JNK as well as iNOS expression in the intestinal mucosa. Oral supplementation of fructooligosaccharides (FOS) or dead Lacobacilli increased the production of ROS of intestine and decreased IL-1β expression of Kupffer cells in STZ and Ins2Akita mice. Feeding of L-NAME, an iNOS inhibitor, but not D-NAME increased the production of ROS of intestinal mucosa and decreased endotoxin in portal vein and IL-1β expression of Kupffer cells in STZ mice. Oral feeding of N-Acetylcysteine, a ROS scavenger, decreased ROS production and inhibited the effects of FOS as well as L-NAME on reversing DM-induced ICAM expression of liver. Using STZ JNK1-/- and Ins2Akita JNK1-/- mice to reverse DM-induced pJNK expression of intestinal mucosa induced a significant decrease of IL-1β expression of Kupffer cells and ICAM expression of liver. Collectively, diabetes induces systemic inflammation through decreasing ROS production and increasing pJNK expression of intestine. Increasing intestinal ROS production could reverse diabetes-induced systemic inflammation.