Elevated Post-Translational Modification of Proteins by O-Linked N-Acetylglucosamine in Various Tissues of Diabetic Goto-Kakizaki Rats Accompanied by Diabetic Complications

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Abstract
We aimed to examine the changes of O-GlcNAc modification of proteins in diabetes, especially in the pathogenesis of diabetic complications. The expression of O-GlcNAc-modified proteins and O-GlcNAc transferase was examined by Western blot analysis and immunohistochemically in various tissues (sciatic nerve, kidney, retina, liver, skeletal muscle, white adipose tissue, skin) of diabetic Goto-Kakizaki (GK) rats and nondiabetic Wistar rats. In the diabetic GK rats the Western blot bands of sciatic nerve, kidney and liver increased in the intensity. In all of the tissues of the non-diabetic Wistar rats, the O-GlcNAc and O-GlcNAc transferase immunoreactivities were observed in almost all cells, with strong expression indicated in the nucleus and weak expression in the cytoplasm. In the diabetic GK rats, these immunoreactivities in the sciatic nerve, kidney, and liver increased in intensity. In these tissues, morphological abnormalities were also observed at both light and electron microscopic levels. In contrast, the Western blot bands and immunoreactivities in the other tissues did not change in the diabetic GK rats. Furthermore, no morphological changes were observed in these tissues. These results indicate that elevated O-GlcNAc modification of proteins may be involved in the diabetic complications seen in diabetic GK rats.