The Effects Of Fermented Cordyceps Mycelium On Oxidative Stress And Glucose Metabolism In Rats With Insulin Resistance

In recent years,the incidence of chronic metabolic diseases is rising rapidly,and insulin resistance(IR)is the key factor for its occurrence and development.Fermented cordyceps mycelium(CM)has biological activities such as hypoglycemic,hypolipidemic and improving immunity,but its specific mechanism still needs further exploration.The aim of this study is to investigate the effects of CM on oxidative stress,glucose metabolism,lipid metabolism and protein metabolism in insulin resistant rats.Forty male Wistar rats were randomly divided into 5 groups,the control group(C,normal diet),the model group(IR group,high fat diet,intraperitoneal injection of 0.80 mg/kg body weight DEX),CM1(high fat feed with 1.65 g/kg CM,intraperitoneal injection of equal amount of DEX),CM2(high fat feed with 3.30 g/kg CM,intraperitoneal injection of equal amount of DEX),CM3(high fat feed with 6.60 g/kg CM,intraperitoneal injection of equal amount of DEX),the rats in group C were injected with equal amount of normal saline.Weekly weight was recorded,after modeling,overnight fasting for 12 h to performe the oral glucose tolerance test,the metabolic status of rats were monitored by CLAMS system,taking blood,liver,muscle and pancreas,assaying redox related indicators,the content of blood lipid,liver glycogen and muscle glycogen,the mRNA expression of genes in pancreas,liver and skeletal muscle were assayed by RT-RCR,the protein expression of nuclear transcription factor 2(Nrf2),phosphoinositide 3-kinase(PI3K),protein kinase B(Akt),phosphorylated protein kinase B(pAkt)and mammalian rapamycin(mTOR)were measured by Western blot.The level of fasting blood glucose,fasting insulin and blood lipid in the IR group were significantly increased,after CM intervention,the level of fasting blood glucose,fasting insulin and blood lipid were significantly decreased in IR rats.And the oxidative stress level was significantly decreased,and the expression of antioxidant related genes were up-regulated in liver and muscle,the expression of endoplasmic reticulum stress and apoptosis related genes were down-regulated,insulin secretion related genes was up-regulated in pancreas,the contents of TG and TC decreased significantly,the expression of lipid synthesis and inflammatory related genes decreased,the expression of lipid decomposition related genes increased,and the expression of gluconeogenesis related genes decreased,the expression of IRS-1,PI3 K and Akt increased,the content of glycogen increased in liver,the expression of PI3 K,Akt,Glut4 and protein synthesis related genes increased,the expression of protein decomposition decreased,and the content of glycogen increased in skeletal muscle.Most of these results were best in the CM3 group.The level of oxidative stress in IR rats increased,damaged islet beta cells and inhibited the activity of PI3K/Akt in the insulin signaling pathway,liver gluconeogenesis and liver glycogen decomposition increased,glucose utilization reduced,decomposition of muscle glycogen and protein accelerated,muscle tissue was damaged,led to the increase of blood glucose in the circle.CM could improve insulin resistance possibly through improving lipid metabolism,alleviating oxidative stress and inflammation,protecting islet beta cells,improving the activity of PI3K/Akt in the insulin signaling pathway in liver and muscle,inhibiting liver gluconeogenesis and muscle decomposition,increasing glucose utilization.