D-ribose Is Related To Glycated Serum Protein And Triglyceride

Objective: D-Ribose,an aldopentose,is active in the glycation of proteins result in rapidly producing advanced glycation end products(AGEs),leading to cell death and cognitive impairment in mice.Glycated serum protein(GSP)is a short-term biomarker for glycemic control in diabetes mellitus,reflecting the average of blood glucose around two weeks.As previous work,D-ribose was abnormally increased in both diabetic patients and ZDF-rats with fatty liver,and contributed to glycated hemoglobin.However,whether D-ribose has effects on GSP and is related to lipid metabolism are unclear.Here,we aimed to identify the contribution of D-ribose to GSP compared with that of D-glucose,and to clarify the role of D-ribose involved in the synthesis of hepatic triglyceride.It will provide us a novel insight to understand more about the development of diabetes and fatty liver,helping prevent and treat metabolic syndrome.Methods: We incubated human serum albumin(HSA,150 μM)and bovine serum albumin(BSA,150 μM)with 20 mM D-ribose compared to 20 mM and 1.0 M D-glucose,and monitored glycation products through specific fluorescence of AGEs,and analyzed the first order rate constant of glycation reaction with Tsou’s kinetic method,and determined the modification lysine residues on glycated HSA/BSA using mass spectrometry.We also intraperitoneally injected SD rats with D-ribose /saline/D-glucose fordetermination of GSP by NBT assay,and investigated the correlativity of D-ribose with GSP in diabetic patients.In further,we detected the levels of urine D-ribose and triglyceride in participants with and without fatty liver by HPLC and kits,respectively.After two weeks intraperitoneally injection of D-ribose /saline to/D-glucose SD rats,we measured concentrations of triglyceride,DGAT and leptin in the liver by kits,and observed pathological performance of liver tissues with HE and oil red O stainings.Results: The results showed that the yield of D-ribose-glycated products was more than those of D-glucose-glycated products in a 2-week incubation of HSA/BSA.The first order rate of 20 mM D-ribose was quicker than that of both 20 mM and 1.0M D-glucose.LC-MS/MS revealed that 17 and 7 lysine residues on HSA were modified by 20 mM D-ribose and 1.0 M D-glucose,respectively.The injection of D-ribose significantly increased the GSP levels in SD rats,but the injection of D-glucose did not.In type 2 diabetic patients,both serum D-ribose and urine D-ribose were positively correlated to GSP,and were prominently higher than controls.Moreover,the urine D-ribose levels were not only positively correlated with serum triglyceride in participants,but also markedly elevated in those with fatty liver.Compared by saline-treated rats,D-ribose-treated rats got notable elevations of hepatic DGAT(both DGAT1 and DGAT2)and leptin,followed by a remarkable increase of hepatic triglyceride,and both of their relative vacuolar areas and numbers of lipid droplets were elevated under HE and oil red O stainings,respectively.Whereas,D-glucose-treated rats had nosignificant biochemical and pathologic changes under the same experimental conditions.Conclusion: Compared with D-glucose,D-ribose is also an important contributor to GSP result from its nonnegligible glycation role in diabetes mellitus.D-Ribose increases the synthesis of hepatic triglyceride via upregulation of DGAT1 and DGAT2,involving in hepatocellular steatosis.