Non-enzymatic glycosylation reaction contributes to a rise of blood glucose in alloxan-induced diabetic rats

ABSTRACT

Non-enzymatic glycosylation reaction, which proceeded at an accelerated rate in diabetes, directly caused sharp diminution of total haemoglobin due to glycosylated proteins including haemoglobin digested by macrophages. The diminution contributed to hypoxia of tissue that repressed the enzymatic activities in the respiratory chain as well as in the tri-carboxylic acid cycle [TCA] and Embden-Meyerhof-Parnas [EMP] pathways. It was postulated that non-enzymatic glycosylation reaction accelerated the rise of blood glucose. The theory was further proven by the hypoglycaemic activities of the extract from Tremella aurantialba broth [TBE]. TBE inhibited the formation of advanced glycosylation end-products [AGEs] in vitro [IC[50] =1.7 mg/ml] and in vivo. TBE, when given in vitro, increased the concentration of total haemoglobin and supply of oxygen, enhanced respiration of tissue, decreased the levels of NADH, speeded up catabolism of glucose and finally generated significant anti-hyperglycaemic and hypoglycaemic effect on alloxan-induced diabetic rats. In addition it elevated plasma insulin level. Oral administration of TBE [100 mg/Kg bw] once a day for 4 weeks resulted in significant reduction in the plasma levels of glucose, fructosamine and the ratio of glycosylated haemoglobin to total haemoglobin. Moreover, oral administration of TBE increased the total haemoglobin and plasma insulin levels and enhanced some key enzymatic activities of EMP, TCA pathways and respiratory chain in the blood of diabetic rats compared with control