The Effect And Mechanism Of Ribose On Glucose And Insulin Metabolism

Objective: Diabetes mellitus is a group of metabolic disorder syndromes characterized by absolute or relative insufficiency of insulin and reduced sensitivity of target organs to insulin.The current view is that dysregulation of glucose metabolism is the main pathological feature of diabetes.This laboratory has been engaged in long-term research on ribose,and has proved in vitro experiments,cell experiments,animal experiments and clinical studies that the glycosylation capacity of ribose is significantly stronger than that of glucose,and it can rapidly undergo non-enzymatic glycation reactions(NEG)with proteins to generate advanced glycation end products(AGEs).The level of ribose in the urine of diabetic patients was significantly higher than that of the normal control group,indicating that diabetic patients had both glucose and ribose metabolism disorders.In order to further elucidate the role of ribose in the occurrence and development of diabetes,the authors explored the relationship between ribose and glucose and insulin metabolism at the cellular level and animal level,and made a preliminary discussion of its mechanism.Methods: The author first incubated different concentration gradients of ribose solutions with mouse neuroblastoma cells(N2a)for 8,12,24,and 48 hours,respectively,and used the CCK8 detection kit to explore the effects of ribose on cell viability;the levels of AGEs and insulin signaling pathway-related proteins were detected by Western blot technology in N2 a cells after 24 hours of ribose incubation;the 2-NBDG probe method was used to study the changes in the glucose uptake ability of N2 a cells after 24 hours of ribose incubation,and then discussed whether ribose would affect the uptake of glucose by cells.In animal experiments,the author performed intraperitoneal injection administration molding on mice with 4 g/kg dose of ribose and 4.8g/kg dose of glucose.Intravenous glucose tolerance tests(IGTT)were performed 14,30 and 45 days after intraperitoneal ribose injection to explore whether ribose affected the glucose tolerance of mice,and insulin tolerance test(ITT)was performed at an interval of 4 days after the 3rd IGTT test to compare whether there were differences in insulin sensitivity between groups;the levels of ribose in various tissues of mice were detected by high performance liquid chromatography(HPLC),and the levels of AGEs were detected by ELISA kit to determine whether there was a disturbance in ribose metabolism and abnormal accumulation of AGEs in mice;Western blot detected the expression levels of insulin signaling pathway-related proteins in mouse skeletal muscle,and preliminarily explored the mechanism of insulin resistance in ribosomal mice;the pathomorphism of kidney,muscle and pancreas were stained by hematoxylineosin.Finally,the authors examined urine ribose levels and AGEs levels in individual organs in GK rats in animal models of spontaneous type 2 diabetes,with a view to using ribose as a therapeutic target for the treatment of type 2diabetes.Results: The high concentration of ribose had a significant toxic effect,the viability of N2 a cells decreased significantly after 40 m M ribose incubation for24 hours,and the content of intracellular AGEs increased;WB results showed that the protein molecules related to insulin signaling pathways in cells and their phosphorylation levels also changed after 24 hours of ribose incubation,mainly due to the decrease in IGF 1R expression,and the phosphorylation level of AKT at site 473 increased;The results of the flow cytometry show that after 24 hours of ribose incubation,the cell’s ability to uptake glucose is significantly reduced.The IGTT and ITT experiments of mice showed that after 45 days of continuous intraperitoneal injection of ribose,the mice had significant diabetic symptoms such as impaired glucose tolerance and reduced sensitivity to insulin;the results of HPLC and ELISA showed that the levels of ribose and AGEs in the kidneys,skeletal muscle,hippocampus and cortex of the ribosyl group mice were abnormally increased;the results of Western blot showed that ribose affected the expression of proteins such as AKT and GLUT4 in the insulin signaling pathway of mouse skeletal muscle,resulting in insulin resistance in mice;HE staining results suggest that the skeletal muscle and kidney tissue of ribosyl group mice have morphological and structural changes.The level of ribose and glucose level in the urine of GK rats was significantly increased,and the level of AGEs in different tissues was inversely correlated with the level of TKT.Conclusion: Ribose inhibits the uptake of glucose by N2 a cells;ribose causes mice to have typical diabetic symptoms such as impaired glucose tolerance and reduced sensitivity to insulin,which may have important pathological significance for the occurrence and development of diabetes;GK rats have dysregulation of ribose and glucose metabolism,which can be used as an animal model for diabetic ribose-related studies...