Role Of Advanced Glycation End Products On Glucose Metabolism In Diabetic Mice Livers, Freshly Isolated Mice Hepatocytes And Cultured Human Hepatocytes

In this study, the effects of advanced glycation end products(AGE) on glucose metabolism in liver have been investigated on three levels.(1) In vitro: 50g/l bovine serum albumin(BSA) was incubated with 10,30,50mmol/l D-glucose at 37℃ for 20,50,70,90 and 140 days, respectively. After incubation, their results were obtained by brown reaction, fluorescence reaction, fructosamine reaction, enzyme-linked immunosorbent assay(ELISA) and sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE). The results indicate that a positive correlation exists between AGE and the concentration of glucose as well as time of incubation.(2)Animal level: Alloxan was used to obtain experimental diabetic mice. After 14,28,42,70 days, the diabetic and control mice was sacrificed to detect fasting glucose, total protein, aminotransferase, glucose tolerance test, AGE in serum; fasting glucose, total protein in urine; and ATPase, malondialdehyde (MDA), succinate dehydrogenase(SDH), glycogen, reduced glutathione(GSH) in liver. It was shown that accumulation of AGE in diabetic mice liver was due to the period of pathological process; the activities of aminotransferase increased and glycogen, GSH, ATPase, SDH disturbed compared with control. Dysfunction of hepatic glucose metabolism and depletion of anti-oxidants occurs at accelerated rates in diabetic mice.(3)Cell level: Freshly isolated mice hepatocytes and cultured human hepatocytes were treated with AGE, glucose and insulin respectively. The incubation of these two hepatocytes with 40,50mmol/l glucose and 20g/l AGE led to the reduction of glycogen, GSH; the enhancement of aminotransferase in these two hepatocytes, and the decreased activities of ATPase, SDH in isolated mice hepatocytes. The function of insulin should have activated hepatocytes to ingest glucose and glyconeogenesis. But the existence of AGE suppressed this function.Based on the above results, it is concluded that the formation of AGE has a positive correlation with glucose and reaction period of time both in vitro and in vivo. The interaction of AGE and glucose may induce the dysfunction of experimental diabetic mice liver, hepatic glucose metabolism and depletion of anti-oxidants in these two hepatocytes above. It could be considered that not insulin but the deposit of AGE is the point of dysfunction of liver in diabetic complications.