Assessment of Oral Glycine and Lysine Therapy on Receptor for Advanced Glycation End Products and Transforming Growth Factor Beta Expression in the Kidney of Streptozotocin-Induced Diabetic Rats in Comparison with Normal Rats

Background & Aims: Today, diabetic nephropathy is considered to be one of the most common causes of end stage renal disease. Uncontrolled hyperglycemia, and consequently, production of advanced glycation end products activate pathways which play key roles in diabetic nephropathy. Among these pathways, high expression of receptor for advanced glycation end products (RAGE) and transforming growth factor beta (TGFβ) are notable. In this study, in order to find compounds which can prevent the incidence or progression of diabetic nephropathy, we examined the effects of glycine and lysine amino acids on expression of RAGE and TGFβ in kidney tissue of diabetic rats. Methods: After rendering rats with diabetes with streptozotocin (STZ), they were divided into different groups and were treated with oral ۱% glycine and ۰.۱% lysine in drinking water for ۱۲ weeks. Blood glucose and serum AGEs were measured during this time. Changes in RAGE and TGFβ expression were assessed by semi quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Results: Results show that both glycine and lysine administration for ۱۲ weeks not only caused a significant reduction in blood glucose and AGEs in diabetic rats, but also led to a significant reduction in RAGE and TGFβ expression in comparison to non-treated diabetic rats. Conclusion: These results show that oral glycine and lysine, as chemical chaperones, have the ability to prevent diabetic nephropathy by decreasing RAGE and TGFβ expression. This may be due to the effect of these chemical chaperones in the reduction of hyperglycemia and serum AGEs in diabetic rats. Since the positive effects of these amino acids in diabetic nephropathy have been observed in previous studies, the determination of their dose in future studies seems necessary

Keywords:

Receptor for advanced glycation end products (RAGE) , Advanced glycation end products (AGEs) , Glycine , lysine , Chemical chaperones