Incretins Increase the Tissue Level of Endogenous Antioxidants in Experimental Diabetes Mellitus

Abstract

Diabetes‐induced angiopathy is caused by chronic hyperglycemia via increased tissue level of free radicals. A decrease in the tissue levels of free radicals or elevation of the tissue concentration of endogenous antioxidant defense system can prevent or delay diabetes‐induced complications. The aim of the study was to examine the effect of incretins on selected markers of the antioxidant system (catalase, dismutase and glutathione reductase) in streptozotocin‐induced diabetic rats using immunohistochemical techniques. The extent of glutathione peroxidase gene expression was also determined in the pancreas of control and GLP‐1 or exenatide‐treated rats. The administration of GLP‐1 and exenatide caused large and significant (p<0.05) increases in the number of catalase‐immunopositive cells in incretin‐treated rats when compared to untreated diabetic controls. The percentage number of glutathione reductase‐ and dismutase‐immunoreactive cells was significantly increased (p<0.05) in diabetic animals treated with either GLP‐1 or exenatide compared to those of untreated diabetic rats. Morphological studies showed that catalase, dismutase and glutathione reductase co‐localized with insulin in pancreatic beta cells. GLP‐1 and exenatide caused marked (p<0.05) elevations in the tissue level of glutathione peroxidase gene expression when compared to that of untreated control. In conclusion, incretin‐induced increase in the tissue level of endogenous antioxidants may play an important role in the protection of the pancreatic beta cell.