Effects of Chicken Serum Metabolite Treatment on the Blood Glucose Control and Inflammatory Response in Streptozotocin-Induced Type 2 Diabetes Mellitus Rats

Chickens can live healthy without adverse effects despite high blood glucose levels. However, the blood biomolecules responsible for maintaining chronic hyperglycemia are unknown. Here, the effects of chicken serum metabolite treatment on blood glucose control and inflammatory response in streptozotocin (STZ)-induced Type 2 Diabetes Mellitus (T2DM) rats were investigated. First, chicken serum treatment reduced the advanced glycation end-products (AGEs) and blood glucose levels in STZ-induced T2DM rats. Second, insulin/glucose-induced acute hypoglycemic/hyperglycemic chickens and the blood biomolecules were screened via nontargeted ultra-performance liquid chromatography with mass spectroscopy (UPLC-MS), identifying 366 key metabolites, including DL-arginine and taurine, as potential markers for chronic hyperglycemia in chickens. Finally, DL-arginine functions for blood glucose control and inflammatory response were evaluated. We found that DL-arginine reduced the levels of blood glucose and AGEs in STZ-induced T2DM rats. In addition, DL-arginine treatment upregulated the glucose transporter type 4 (GLUT4) expression in the muscles and downregulated the advanced glycation end products receptor-1 (AGER1) expression in the liver and nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) expression in the pancreas and thymus tissues. Overall, these results demonstrate that serum metabolite of DL-arginine could maintain blood glucose homeostasis and suppress the inflammatory response in chickens. Therefore, DL-arginine may be a novel target for developing therapeutic agents to regulate hyperglycemia.