Role Of Fluctuated Glucose On Diabetic Mice Livers And Cultured Human Hepatocytes

With the imprvoment of the living level of people, the diabetes has become one of common ailments which have attracted intensive attentions. Scientists all over the world are studying its pathogenesis and seeking therapy or remedy to treat the patients with diabetes. Hyperglycemia is the symbol and the chief cause of diabetes and its complications. The phenomennon of clinical research show us that the long-term fluctuated blood sugar do more damages than high blood sugar only. The prognosis and all kinds of diabetic complicaitions is not only related to the high blood sugar, but also related to the fluctuation of blood sugar. The liver plays an important role in the substance metabolism especially glucose metabolism and biotransformation such as digestion, absorption, excretion. The liver also plays an important role in the development of diabetes and its complications. But the studies on influence of fluctuated blood sugar on the mice liver and human hepatocytes have not been reported. In this study, the damage effects of fluctuated glucose in liver have been investigated on two levels. This study was designed to.offer experimental basis of diabetes and its complications and to provide theory on measures of control blood sugar.(1) Animal level: Alloxan was used to obtain experimental diabetic mice. Fluctuated glucose mouse model is obtained by injecting glucose through the belly. After 1 month, all groups of mice was sacrificed to detect fasting glucose, fructosamine, aminotransferase, FFA, TC in serum; and glycogen, malondialdehyde (MDA), CAT, AGEs,glutathione(GSH) in liver to differentiate the influence between fluctuate blood sugar and high blood sugar on the livers.. It was shown that the activities of aminotransferase, MDA, AGEs increased and glycogen, GSH, CAT reduced compared with control. Dysfunction of hepatic glucose metabolism, depletion of anti-oxidants and IR occurs at accelerated rates in diabetic mice. The symptom of the fluctuated glucose mice is aggravated compared with the diabetic mice.(2) Cell level: Cultured human hepatocytes were treated with high glucose and fluctuated glucose to detect aminotransferase, GSH, MDA, hepatin, the activities of GK and ATPase, [Ca²⁺]i in vivo in human hepatocyte and the fluidity of cell membrane. High glucose and fluctuated glucose led to the reduction of, the activities of GK, the fluidity of cell membrane; the enhancement of aminotransferase, the activities of ATPase, and [Ca²⁺]i in vivo in human hepatocyte,. Fluctuated glucose do more harm to cells compared with cells treated with high glucose.Based on the above results, it is found that fluctuated glucose do more harm to cells compared with high glucose both in extrocellular and introcellular. The phenomenon extrocellular are likely to be caused by IR, ISI, oxidative stress, the confusion of glucose metabolism and increase of AGEs. The phenomenon introcellular is likely to be caused by the confusion of glucose metabolism,the overload of [Ca²⁺]i, the increase of activity of amino- transferase the decrease of fluidity of cell membrane.