# Hyperglycemia impairs the expression of inflammatory mediators in rat intestine: an implication for intestinal inflammation and inflammatory bowel disease

## TL;DR

This study shows that high blood sugar from diabetes can worsen gut inflammation, linking diabetes to inflammatory bowel disease through immune and metabolic interactions.

## Contribution

The study reveals how chronic hyperglycemia affects intestinal inflammation and macrophage activity, linking diabetes to inflammatory bowel disease.

## Key findings

- Chronic hyperglycemia causes intestinal inflammation and barrier disruption in both small and large intestines.
- Macrophage activation and increased expression of CD68, iNOS, TNF-α, and IL-6 were observed in diabetic rats.
- Female rats showed greater susceptibility to gut inflammation caused by diabetes.

## Abstract

Diabetes mellitus and inflammatory bowel disease are chronic inflammatory disorders characterized by immune dysregulation and rising global prevalence. Epidemiological studies increasingly suggest a bidirectional association between the two conditions, linked through shared mechanisms of intestinal barrier dysfunction, microbial dysbiosis, and sustained innate immune activation. Activated macrophages play a central role in driving mucosal inflammation through polarization toward a pro-inflammatory M1 phenotype, accompanied by increased production of inflammatory cytokines. These mediators disrupt tight junctions, induce epithelial apoptosis, and perpetuate cycles of immune activation and tissue injury. This macrophage–cytokine axis not only amplifies local inflammation but also sustains chronic barrier dysfunction, creating a pathogenic overlap between diabetes mellitus-associated intestinal injury and intestinal bowel disease. In this study, we used a low dose streptozotocin and high-fat diet-induced diabetic Sprague–Dawley rat model in both sexes to investigate the effects of chronic hyperglycemia on intestinal inflammation, with particular emphasis on macrophage activation and pro-inflammatory cytokine responses. We found inflammation in both small and large intestines with mucosal injury and barrier disruption, and immune activation involving macrophages and enhanced expression of CD68, iNOS, TNF-α, and IL-6. Female rats were more susceptible to gut-related inflammatory changes due to diabetes. These findings suggest a complex interplay between epithelial stress, immune signaling, and microbial factors supporting the role of intestinal inflammation in the immune–metabolic interaction in diabetes-associated intestinal changes, which may contribute to the pathogenesis of inflammatory bowel disease.