Up-Regulated Expression of Advanced Glycation End-Products and Their Receptor in the Small Intestine and Colon of Diabetic Rats

Abstract

The expression of AGE and RAGE is up-regulated in the small intestine and colon of diabetic rats. The increased AGE and RAGE levels may contribute to diabetic GI dysfunction.

Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

“…Furthermore, we also found that the AGE and RAGE distributed in the striated muscle and squamous epithelial cells of esophagus and also in the stomach (unpublished data). The present study together with our previous study [21] is the first reports of the localization of AGE and RAGE in the whole rat GI tract. This provides a basis for further comparison study of the distribution of AGE and RAGE on GI tract with diseases, such as diabetes.…”

“…Our previous study [21] showed homogenous AGE distribution in the cytoplasm of smooth muscle cells, epithelial cells, and neurons of the myenteric and submucosal plexus in the layers of colon and small intestine. Furthermore, homogeneous distribution of RAGE was found in epithelial cells and neurons.…”

“…Our previous study showed that the expression of AGE and RAGE was up-regulated in the small intestine and colon of STZ-induced type 1 diabetic rats [21] . STZ rats have high blood glucose but formation of free radicals and STZ cytotoxicity plus its direct effects on AGE formation and RAGE expression in GI tract may be questioned.…”

“…Therefore, they may also play an important role in the diabetic GI tract. In our previous study we demonstrated that AGE [N epsilon-(carboxymethyl)lysine, CML and N epsilon-(carboxyethyl)lysine, CEL] and RAGE were up-regulated in the small intestine and colon of streptozotocin (STZ)-induced diabetic rats [21] . However, to the best of our knowledge, data on the distribution of AGE and RAGE in the GI tract of type-2 diabetes have never been described.…”

Domain I-IV of β2-glycoprotein I inhibits advanced glycation end product-induced angiogenesis by down-regulating vascular endothelial growth factor 2 signaling

“…It is reported that AGE promotes neovascularization by increasing the expression of VEGF (mainly VEGF-A) in endothelial cells and consequently inducing tube formation of the retinal microvessel endothelial cells (23). AGE can potentially induce retinal ganglion cells to express VEGF-A and inhibit apoptosis and are, thus, important in the pathogenesis of diabetic retinopathy (24).…”