|ISSN No. 1606-7754 Vol.15 No.2 August 2007|
Non-enzymatic glycosylation reaction contributes to a rise of blood glucose in alloxan-induced diabetic rats
Zhicai Zhang, Feng-Jie Cui
School of Food Science and Biotechnology, Jiangsu University, Zhenjiang, 212013 P.R. China
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 (IC50 =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. (Int J Diabetes Metab 15: 51-58, 2007)
Keywords: non-enzymatic glycosylation reaction, glycosylated haemoglobin, total haemoglobin, respiration chain, EMP pathway, TCA pathway, Tremella aurantialba
According to the projections of the World Health Organisation the prevalence of diabetes is likely to increase by 35%.1 Currently there are over 150 million diabetics worldwide and this is likely to increase to 300 million or more by the year 2025.1,2 Therefore, it is necessary to look for new targets of therapy and new resources to manage this health problem. Diabetes mellitus (DM) is a chronic disease caused by inherited and/or acquired deficiency in the production and/or the effectiveness of the insulin produced. Such a deficiency results in elevated blood glucose levels which cause an accelerated development of diabetic complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Diabetic complications usually arise as a result of non-enzymatic protein glycation, which leads to the formation of heterogeneous, toxic and antigenic advanced glycation end products (AGEs). Hence, numerous studies have focused on the analysis of the implicated glycated proteins or the AGE-modified circulating proteins, their physiology, and various plants and animal products that inhibit non-enzymatic protein glycation. Very little is known about the increase in blood glucose resulting from non-enzymatic glycosylation reaction. An understanding of this process could help in the development and the therapy of diabetic mellitus and its complications.
Higher Basidiomycetes mushrooms are unlimited sources of anticancer and immunostimulating polysaccharides.3,4 Tremella aurantialba is used for food pharmaceutical product. The polysaccharides from its body and mycelia have many medical functions including relieving cough and reducing phlegm, decreasing blood glucose, curing cardiovascular and cerebral diseases, enhancing haemopoietic function and increasing body’s immunity.5-10 Previous studies have shown that the polysaccharides from mycelia possess hypocholesterolaemic and antihyperglycaemic activities, cure diabetes and its complications as well as control blood fat and blood pressure.7,8
The aim of this study was to examine Hb (O2 carrier) and the enzyme activities of the respiratory chain and catabolic pathways of glucose in normal and diabetic rat. This study was also set to expound the hypothesis that non-enzymatic glycosylation reaction can contribute to the rise of blood glucose in diabetic rats. Finally, the hypothesis was tested with the anti-hyperglycaemic and hypoglycaemic effect of the extract of T. aurantialba broth (TBE), an in vitro and in vivo non-enzymatic glycosylation reaction inhibitor.