Effects Of Polysaccharide From The Fruiting Bodies Of Auricularia Auricular On Glucose Metabolism In Mice With ⁶⁰Co-?-Radiation-Induced Oxidative Stree

Oxidative stress caused by excessive reactive oxygen species?ROS?under the condition of radiation leads to bio-molecular damage,which will ultimately destroy normal cell physiology and affect metabolic processes of lipids and carbohydrates in cells.Oxidative stress is closely related to the development of metabolic diseases such as glucose metabolism disorder.In order to prevent the development of related physiological abnormalities such as glucose metabolism disorder caused by radiation-induced oxidative stress,the treatment strategies including the use of plant-derived natural antioxidants need to be developed.In this study,sulfated neutral Auricularia auricular polysaccharide?SNAAP?was used as the test substance for in vitro study of hypoglycemic effect and in vivo study of the regulation of glucose metabolism in radiated mice to reveal the function of SNAAP in glucose metabolism,which will further provide theoretical support for the therapeutic value of Auricularia auricular polysaccharides.In vitro experiment shows that SNAAP has a hypoglycemic effect by absorbing glucose,inhibiting the activities of?-amylase and?-glucosidase,and inhibiting glucose diffusion.In vivo experiment shows that elevated fasting blood glucose,decreased fasting insulin?FINS?and hepatic glycogen contents,decreased oral glucose tolerance,decreased insulin sensitivity index?HOMA-IS?and islet?-cell function?HOMA-??index,reduced activities of hepatic hexokinase?HK?and pyruvate kinase?PK?,increased activities of hepatic glucose-6-phosphatase?G6Pase?,phosphoenolpyruvate carboxylase?PEPCK?and glycogen phosphorylase?GP?were found in the animal models of oxidative stress induced by ⁶⁰Co-?-radiation,which proves that glucose metabolism disorder exists in radiated mice.SNAAP reduces blood glucose level and regulates glucose metabolism by promoting glycogen synthesis,regulating the activities of enzymes in rate-limiting steps of hepatic glucose metabolism,improving islet cell function,increasing liver insulin sensitivity,and promoting insulin secretion.The activities of superoxide dismutase?SOD?and glutathione peroxidase?GSH-Px?and the content of malondialdehyde?MDA?were increased in the serum,liver and pancreas of radiated mice,which shows the destroyed redox imbalance.Histomorphological observation of liver tissues combined with increased serum alanine aminotransferase?ALT?and aspartate aminotransferase?AST?activities and decreased hepatic insulin sensitivity proved that oxidative stress destroyed the structure and function of the liver in radiated mice;Histomorphological observation of pancreas combined with increased serum amylase?AMS?activity,decreased HOMA-?value and decreased FINS revealed that ROS-induced pancreatic cell dysfunction occurred.SNAAP regulates glucose metabolism by increasing SOD and GSH-Px activities,reducing MDA content,alleviating oxidative damage in organs,and restoring the function of liver and pancreas in radiated mice.Real-time relative quantitative reverse transcription polymerase chain reaction?RT-PCR?and the western blot?WB?techniques were used to measure the expression of related genes and proteins in the pancreas and liver of radiated mice.ROS reduced mRNA expression of PDX-1,GLUT2 and GK in the pancreas of radiated mice.SNAAP can stimulate insulin secretion by down-regulating PDX-1 throngh the elimination of ROS.The mRNA expression of JNK in the liver was increased by radiation-induced oxidative stress.The increased phosphorylation of JNK and the decreased phosphorylation of Akt worked together to inhibit the phosphorylation of FoxO1,which further leaded to an increased expression of PEPCK and G6Pase in the liver of radiated mice and contributed to the enhanced hepatic gluconeogenesis.SNAAP can restore gluconeogenesis to a normal level by eliminating ROS and altering the expression of JNK and its downstream genes and proteins.Besides,increased Akt phosphorylation by SNAAP further phosphorylated the downstream target GSK-3?,thereby attenuating the inhibitory effect of GSK-3?on GYS2 and ultimately promoting glycogen synthesis.In summary,SNAAP can improve the glucose metabolism disorder caused by radiation-induced oxidative stress.This research has important theoretical and practical value for space exploration,the military and the health and safety of people who are subjected to exposure to radiation.