Effects of vanadate on plasma lipoprotein profiles in experimental diabetic rats

The insulin-like effects of vanadate have been intensively studied in the biological system. Lipids and lipoprotein profiles are altered in diabetes. Rats were made diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight) in citrate buffer. After the overt of diabetes, the diabetic rats were treated with sodium orthovanadate (0.3 mg/ml) for fifteen days. The altered cholesterol, phospholipids and triglycerides in plasma lipoprotein fractions (HDL, LDL and VLDL) were found to be reverted back to near normal levels in vanadate treated diabetic rats.     

Effects of high sucrose diet on insulin-like effects of vanadate in diabetic rats

The insulin-like effects of vanadate were compared in streptozotocin-induced diabetic rats fed on high starch control and high sucrose diets for a period of six weeks. Diabetic rats in both diet groups were characterized by hypoinsulinemia, hyperglycemia (6.8–7.0 fold increase) and significant decreases (p<0.001) in the activities of glycogen synthase, phosphorylase and lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme in liver. There were no diet-dependent differences in these abnormalities. However, the insulin-mimetic agent vanadate was more effective in diabetic rats fed sucrose diet as compared to animals fed control starch diet. Vanadate administration resulted in 30% and 64% decreases in plasma glucose levels in diabetic rats fed control and sucrose diets, respectively. The activities of glycogen synthase (active) and phosphorylase (active and total) were restored significantly by vanadate in control (p<0.05–0.01) and sucrose (p<0.001) diets fed diabetic rats. This insulin-mimetic agent increased the activities of hepatic lipogenic enzymes in control diet fed rats to 38–47% of normal levels whereas in sucrose fed group it completely restored the activities. Sucrose diet caused a distinct effect on the plasma levels of triacylglycerol (4-fold increase) and apolipoprotein B (2.8-fold increase) in diabetic rats and vanadate supplementation decreased their levels by 65–75%. These data indicate that vanadate exerts insulin-like effects in diabetic rats more effectively in sucrose fed group than the animals fed control diet. In addition, vanadate also prevents sucrose-induced hypertriglyceridemia.     

Decrease of liver protein kinase C in streptozotocin-induced diabetic rats and restoration by vanadate treatment

Effects of streptozotocin-induced diabetes and administration of the insulinmimetic agent, vanadate in rats on the liver protein kinase C-induced phosphorylation of exogenous C (Histone III-S) and endogenous substrates were investigated. Diabetes caused a significant fall (40-60%) in liver cytosolic protein C activity measured using both types of substrates. Vanadate treatment for a period of 5 weeks restored them to normal levels. Phosphorylation of cytosolic target proteins for protein kinase C followed a similar pattern in response to diabetes and vanadate. These treatments had no effect on particulate protein kinase C activity. Vanadate also had no effect in normal livers with respect to the protein kinase C system.     

Effect of vanadate on tryptophan metabolism in streptozotocin diabetic rats.

Administration of sodium orthovanadate (0.3 mg/ml) through drinking water for 20 days to streptozotocin-induced diabetic rats resulted in reversal of markedly elevated activities of some of the key enzymes of tryptophan-niacin pathway, viz. hepatic and renal aminocarboxymuconate semialdehyde decarboxylase and hepatic tryptophan oxygenase, to normal levels without restoring the elevated blood sugar level to normal state. However vanadate administration to normal rats did not cause any significant change.     

Insulin-like effects of vanadate on glucokinase activity and fructose 2,6-bisphosphate levels in the liver of diabetic rats

Streptozotocin diabetic rats showed more than a 4-fold increase in blood glucose levels, whereas hepatic glycogen, fructose 2,6-bisphosphate concentration, and 6-phosphofructo-2-kinase activity were decreased. The "total" 6-phosphofructo-2-kinase and the "active" (nonphosphorylated) form of the enzyme were decreased to a different extent, resulting in a fall of the "active"/"total" activity ratio. Vanadate administration for a 2-week period restored the altered values in the diabetic rats without modifying significantly in the control animals any of the parameters studied. Glucokinase activity was essentially lacking in the diabetic animals, and vanadate treatment restored the activity to about 65% of its control value, a good correlation between the recovery of the enzyme and the blood glucose level being observed. These results show an insulin-like effect of vanadate in the whole animal and suggest that insulin and vanadate possess similar actions on hepatic intracellular events.     

Effect of vanadate on the metabolism of bile acids in diabetic rats

The effect of treatment with vanadate on the metabolism of bile acids was studied in normal and diabetic rats. In the normal rats, the composition of biliary bile acids was not changed by drinking an aqueous solution of 0.2 g/l NaVO3-5 g/l NaCl ad libitum for two weeks. By contrast, the increased proportion of cholic acid, accounting for 88% of the total biliary bile acids, in the diabetic rats decreased to 46% by the treatment with vanadate without any elevation of serum insulin level. These results indicate that vanadate with an insulin-like effect on glucose metabolism in diabetic rats has such an effect also on bile acid metabolism in an insulin-deficient state.     

Effects of vanadyl sulfate on liver of streptozotocin-induced diabetic rats

The aim of this study was to investigate the microscopic and biochemical effects of vanadyl sulfate on liver tissue of normal and streptozotocin (65 mg/kg) diabetic rats. Vanadyl sulfate was administered by gavage at a dose of 100 mg/kg. Degenerative changes were observed in diabetic animals by light and transmission electron microscopes. Although there were individual differences in diabetic animals to which vanadium was given, some reduction of degenerative changes were detected. After 60 d of treatment, serum aspartate and alanine transaminase, alkaline phosphatase, blood glucose levels, liver lipid peroxidation, and nonenzymatic glycosylation significantly increased, but liver glutathione levels significantly decreased in the diabetic group. On the other hand, treatment with vanadyl sulfate reversed these effects. As a result, it might be concluded that vanadyl sulfate has a protective effect on damage of liver of streptozotocin-induced diabetic rats.     

Insulin-like effects of vanadate and selenate on the expression of glucose-6-phosphate dehydrogenase and fatty acid synthase in diabetic rats

Isulin is capable of regulating cellular and metabolic processes as well as gene expression. In recent years, enthusiasm has surfaced for using insulin mimetics to study the mechanism of action of insulin. Vanadata and selenate are two compounds that have been found to mimic the action of insulin on control to blood glucose levels in vivo. Vanadata has also been shown to regulate the expression of several enzymes both in vivo, however, studies concerning selenate's ability to regulate expression have not been reported. In his study we show that administration of vanadate or selenate to streptozotocin-induced diabetic rats not only normalizes blood glucose levels similarly to insulin but also positively affects the expression of two key metabolic enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS). Both G6PDH and FAS activity are significantly decreased in diabetic animals compared to non-diabetic control. Treatment of the diabetic animals with either insulin, vanadate or selenate restored both activities to about 80–90% of control. All treatment conditions exhibited activities significantly higher than those determined for the diabetic group but did not differ significantly from each other. Increases in GPDH or FAS activity are due to increases in mRNA level. Increase in both G6PDH and FAS mRNA was comparable to the observed increase in activity suggesting that regulation of expression by the mimetics occurs pretranslationally.     

Effects of vanadate on the cyclic AMP-protein kinase system in rat liver

Vanadate produced a marked increase of cyclic AMP levels in rat liver slices; a parallel scheme of variation was found in the case of protein kinase activity. Similar trends of variations were observed in in vivo experiments. These results support the idea that vanadate can affect the cyclic AMP-protein kinase system and moreover, due to the function of liver (an organ considered to play a fundamental role in the general metabolism in mammals) the same results add more data in support for a general regulatory role for vanadate.     

恩施绿茶茶多糖对糖尿病模型大鼠血糖的影响

目的:研究恩施绿茶茶多糖对糖尿病模型大鼠血糖的影响。方法:用四氧嘧啶(alloxan)建立糖尿病模型大鼠,行恩施绿茶茶多糖灌胃4周,观察糖尿病大鼠血糖(FBG)、胰岛素(INS)、肝葡萄糖激酶(GK)、血清中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)以及脾脏、胸腺系数的变化。结果:恩施绿茶茶多糖能明显降低糖尿病大鼠的FBG,增强GK、SOD和GSH-Px的活性,减少MDA的含量,升高脾脏、胸腺系数。结论:恩施绿茶茶多糖具有降血糖,抗氧化和增强机体免疫功能的作用。     

Comparison of biochemical properties of liver arginase from streptozocin-induced diabetic and control mice

Arginase activity is elevated in livers of diabetic animals compared to controls and there is evidence that this is due in part to increased specific activity (activity/mg arginase protein). To investigate the molecular basis of this increased activity, the physicochemical and kinetic properties of hepatic arginase from diabetic and control mice were compared. Two types of arginase subunits with molecular weights of 35,000 and 38,000 were found in both the diabetic and control animals and the subunits in these animals had similar, multiple ionic forms. Kinetic parameters of purified preparations of arginase for arginine (apparent Km and Vmax values) and the thermal stability of these preparations from diabetics and controls were also similar. Furthermore, no difference was found in the distribution of arginase activity among different subcellular liver fractions. Separation of basic and acidic oligomeric forms of arginase by fast-protein liquid chromatography resulted in a slightly different distribution of activity among the forms in the normal and diabetic group. The apparent Km values for Mn2+ of the basic form of the enzyme were 25 and 33 microM for the enzyme from normal and diabetic animals, respectively; for acidic forms, for which two apparent Km values were measured, the values were 8 and 197 microM for arginase from controls and 35 and 537 microM from diabetics. These results indicate that in diabetes, while no marked changes in the physicochemical characteristics of arginase are obvious, some changes are found in the interaction of arginase with its cofactor Mn.     

Immunohistochemical localisation of arginase in human liver using monoclonal antibodies against human liver arginase

Monoclonal antibodies against human liver arginase were raised in order to determine the exact distribution of arginase in human liver using a modified indirect unlabelled immunoperoxidase method. In normal human liver specific immunohistochemical staining was found in the cytoplasm of hepatocytes. Portal components (bile ducts and veins) and fibrous tissue were non-reactive, while erythrocytes were slightly positive. The specificity of the immunological reaction was confirmed by control tests. Spectrophotometry was used to quantitate the immunohistochemical reaction product, and the results indicated that arginase is homogeneously distributed in the liver lobule.     

Immunohistochemical localisation of arginase in human liver using monoclonal antibodies against human liver arginase

Summary Monoclonal antibodies against human liver arginase were raised in order to determine the exact distribution of arginase in human liver using a modified indirect unlabelled immunoperoxidase method. In normal human liver specific immunohistochemical staining was found in the cytoplasm of hepatocytes. Portal components (bile ducts and veins) and fibrous tissue were non-reactive, while erythrocytes were slightly positive. The specificity of the immunological reaction was confirmed by control tests. Spectrophotometry was used to quantitate the immunohistochemical reaction product, and the results indicated that arginase is homogeneously distributed in the liver lobule.Present address: Biologisches Institut der Universität Stuttgart, Ulmerstrasse 227, D-7000 Stuttgart 60, Federal Republic of Germany