Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes

The role of rutin on carbohydrate metabolism in normal and streptozotocin (STZ)-induced diabetic rats was investigated in the present study. Administration of STZ led to a significant (p <0.05) increase in fasting plasma glucose and a decrease in insulin levels. The content of glycogen significantly (p <0.05) decreased in liver and muscle, but increased in kidney. The activity of hexokinase decreased whereas the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly (p <0.05) increased in the tissues. Oral administration of rutin (100 mg/kg) to diabetic rats for a period of 45 days resulted in significant (p <0.05) alterations in the parameters studied but not in normal rats. A decrease of plasma glucose and increase in insulin levels were observed along with the restoration of glycogen content and the activities of carbohydrate metabolic enzymes in rutin-treated diabetic rats. The histopathological study of the pancreas revealed the protective role of rutin. There was an expansion of the islets and decreased fatty infiltrate of the islets in rutin-treated diabetic rats. In normal rats treated with rutin, we could not observe any significant change in all the parameters studied. Combined, these results show that rutin plays a positive role in carbohydrate metabolism and antioxidant status in diabetic rats.     

Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta

The aim of this study was to investigate the protective effects of vanadyl sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals.     

Effect of exposure to diabetic and fasted plasma on glucose oxidation in rat aorta

Glucose metabolism is depressed in aortic intima-media of fasted and diabetic rats. The aim of this study was to elucidate the influence of diabetic and fasted plasma on glucose oxidation in rat aorta. Male Sprague-Dawley rats weighing about 200 g were used. Diabetes was induced by streptozotocin (65 mg/kg) and the rats were used after a diabetes duration of two weeks. Fasted rats were used after food deprivation for 3 days. Aortic intima-media was preincubated in plasma for 120 or 240 min. During a further incubation for 2 hours in Krebs-Henseleit bicarbonate buffer the oxidation of 14C-glucose to 14CO2 was measured. Preincubation of normal aorta in diabetic or fasted rat plasma and diabetic human plasma significantly depressed the subsequently determined glucose oxidation in comparison to aorta preincubated in normal plasma. Preincubation of aorta from diabetic or fasted rats in normal rat plasma enhanced the glucose oxidation compared with the glucose oxidation in aorta of diabetic or fasted rats after preincubation in the corresponding plasma. These results suggest that diabetic and fasted plasma contains factor(s) which in vitro depress glucose oxidation in vascular smooth muscle and, thus, may be of importance for the lowered glucose oxidation found in vascular smooth muscle preparations obtained from diabetic or fasted animals.     

Effects of serpasil on lipids,lipoprotein lipase and lipogenic enzymes in alloxan diabetic rats

Diabetes intensifies the development of atherosclerosis. Treatment with antihypertensive drug, serpasil, arrested the progression of atherosclerosis in alloxan diabetic rats by significantly decreasing the concentration of cholesterol, phospholipids and triglycerides of serum, liver, kidney and aorta. Serpasil also decreased fasting blood sugar and urine sugar levels in these rats. Serpasil administration remarkably altered the deranged lipid metabolism in alloxan diabetic rats by nearly restoring the lipolytic and lipogenic enzyme activity to that of the normal     

Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging.

It is unclear at present whether specific mtDNA point mutations accumulate during normal human aging. In order to address this question, we used quantitative PCR of total DNA isolated from skeletal muscle from normal individuals of various ages to search for the presence and amount of spontaneous mtDNA point mutations in two small regions of the human mitochondrial genome. We observed low levels of somatic mutations above background in both regions, but there was no correlation between the amount of mutation detected and the age of the subject. These results contrasted with our finding of an age-related increase in the amount of the mtDNA "common deletion" in these very samples. Thus, it appears that both somatic mtDNA point mutations and mtDNA deletions can arise at low frequency in normal individuals but that, unlike deletions, there is no preferential amplification or accumulation of specific point mutations in skeletal muscle over the course of the normal human life span.     

Hypothalamic Catecholamine Metabolism in Diabetic Rats: The Effect of Insulin Deficiency and Meal Ingestion

The effect of moderate insulin deficiency of 2 weeks in duration on hypothalamic catecholamine metabolism in food-deprived and meal-fed rats was evaluated. Hypothalamic tyrosine content in food-deprived (from 0700 to 1600 h), diabetic rats was normal. Also normal were the rates of 3,4-dihydroxyphenylalanine accumulation following aromatic amino acid decarboxylase inhibition, norepinephrine and 3,4-dihydroxyphenylethylamine (dopamine) clearance after tyrosine hydroxylase inhibition, and intraneuronal amine accumulation following monoamine oxidase inhibition. Differences in hypothalamic amine metabolism were apparent, however, when diabetic and normal rats were fed 2-g meals. The 3-methoxy-4-hydroxyphenylethyleneglycol sulfate accumulation rate was depressed in diabetic rats by the carbohydrate meal but was stimulated by the tyrosine-supplemented protein meal. In contrast, the tyrosine-supplemented diet had no effect on 3,4-dihydroxyphenylacetic acid accumulation in diabetic animals, whereas the production rate in normal rats was increased. We conclude that normal responses occurring in hypothalamic catecholamine metabolism after the consumption of a meal are modified by the presence of diabetes.     

Tissue Response to a Supplement High in Aluminum and Silicon

The objective was to determine the effects of sodium zeolite A (SZA) on mineral metabolism and tissue mineral composition in calves. Twenty calves were placed on study at 3 days of age and were placed into one of two groups: SS, which received 0.05% BW SZA added to their milk replacer, and CO, which received only milk replacer. Blood samples were taken on days 0, 30, and 60 for mineral analysis. Urine and feces were collected on day 30 for mineral metabolism, and on day 60, the calves were euthanized, and samples were taken from numerous organs for mineral analyses. Aluminum retention was increased in the SS calves (p = 0.001). Silicon concentrations were increased in the aorta, spleen, lung, muscle, and kidney of the SS calves, and aluminum was increased in all SS tissues (p < 0.05). Calcium concentrations were increased in aorta, liver, muscle, and tendon; phosphorus concentrations were increased in aorta, but decreased in plasma; magnesium concentrations were increased in aorta, heart, kidney, liver, and pancreas, but decreased in plasma; and iron concentrations were decreased in kidney and liver (p < 0.05). The accumulation of tissue aluminum and therefore potential adverse consequences may preclude any benefits of using SZA as a dietary supplement.     

Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats

In this study, we investigated the efficiency of short-term treatment with gemfibrozil in the reversal of diabetes-induced changes on carbohydrate and lipid metabolism, and antioxidant status of aorta. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). After 12 weeks of induction of diabetes, the control and diabetic rats were orally gavaged daily with a dosing vehicle alone or with 100 mg/kg of gemfibrozil for 2 weeks. At 14 weeks, there was a significant increase in blood glucose, plasma cholesterol and triglyceride levels of untreated-diabetic animals. Diabetes was associated with a significant increase in thiobarbituric acid reactive substances (TBARS) in both plasma and aortic homogenates, indicating increased lipid peroxidation. Diabetes caused an increase in vascular antioxidant enzyme activity, catalase, indicating existence of excess hydrogen peroxide (H₂O₂). However, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities in aortas did not significantly change in untreated-diabetic rats. In diabetic plus gemfibrozil group both plasma lipids and lipid peroxides showed a significant recovery. Gemfibrozil treatment had no effect on blood glucose, plasma insulin and vessel antioxidant enzyme activity of diabetic animals. Our findings suggest that the beneficial effect of short-term gemfibrozil treatment in reducing lipid peroxidation in diabetic animals does not depend on a change of glucose metabolism and antioxidant status of aorta, but this may be attributed to its decreasing effect on circulating lipids. The ability of short-term gemfibrozil treatment to recovery of metabolism and peroxidation of lipids may be an effective strategy to minimize increased oxidative stress in diabetic plasma and vasculature.     

Increased aortic stiffness in the insulin-resistant Zucker fa/fa rat

Accumulating clinical evidence indicates increased aortic stiffness, an independent risk factor for cardiovascular and all-cause mortality, in type 2 diabetic and glucose-intolerant individuals. The present study sought to determine whether increased mechanical stiffness, an altered extracellular matrix, and a profibrotic gene expression profile could be observed in the aorta of the insulin-resistant Zucker fa/fa rat. Mechanical testing of Zucker fa/fa aortas showed increased vascular stiffness in longitudinal and circumferential directions compared with Zucker lean controls. Unequal elevations in developed strain favoring the longitudinal direction resulted in a loss of anisotropy. Real-time quantitative PCR and immunohistochemistry revealed increased expression of fibronectin and collagen IV alpha 3 in the Zucker fa/fa aorta. In addition, expression of transforming growth factor-beta and several Smad proteins was increased in vessels from insulin-resistant animals. In rat vascular smooth muscle cells, 12-18 h of exposure to insulin (100 nmol/l) enhanced transforming growth factor-beta1 mRNA expression, implicating a role for hyperinsulinemia in vascular stiffness. Thus there is mechanical, structural, and molecular evidence of arteriosclerosis in the Zucker fa/fa rat at the glucose-intolerant, hyperinsulinemic stage.     

Carbohydrate metabolism in Manduca sexta during late larval development

The carbohydrate metabolism in Manduca sexta underwent significant changes during late larval development. Approximately 10% of fat body glycogen phosphorylase was active during the feeding period of the 5th instar, pharate-pupal development and after the pupal moult; it is concluded that glycogen synthesis prevailed. During the last larval and the pupal moult, as well as the wandering stage the percentage of active phosphorylase was significantly increased indicating that fat body glycogen stores were broken down to supply substrates to meet the demands of carbohydrate metabolism. In the course of the last larval moult and the wandering stage the fat body glycogen content decreased significantly from about 300 to about 200 μg mg⁻¹ dry mass substantiating that carbohydrates were released from the fat body. Prior to phosphorylase activation, the concentrations of total haemolymph sugars decreased significantly from about 12 to about 6 mg trehalose equivalents ml⁻¹ (last larval moult) and from about 18 to about 12 mg ml⁻¹ (wandering stage), and increased again slightly when phosphorylase was activated. The haemolymph glucose concentration decreased significantly from about 1.1 to 0.3 mg ml⁻¹ (last larval moult) and in the course of the 5th-instar feeding period from about 1.1 to 0.2 mg ml⁻¹, and remained at this level until the beginning of adult development. The amount of chitosan present in the cuticle increased steadily during the feeding period of the 5th instar from about 10 to 110 mg. It appears that fat body glycogen might be broken down during the last larval moult and the wandering period to provide substrates for chitin synthesis. A dramatic decrease in the amount of chitosan was observed prior to the pupal moult.     

Activity and localisation of sucrose synthase and invertase in ovules of sexual and apomicticBrachiaria decumbens

Summary Brachiaria decumbens has sexual and apomictic reproduction. Apomixis is facultative and of the aposporic type. In early stages of ovule development, differences in the pattern of callose deposition between sexual and apomictic plants were observed which points to possible differences in carbohydrate metabolism. Therefore, a comparative study on carbohydrate metabolism between a sexual diploid ecotype and an apomictic tetraploidB. decumbens was made. A histochemical determination of two enzymes responsible for sucrose degradation, sucrose synthase and invertase, was performed for all stages of ovule development. In addition, the concentrations of sucrose, glucose, and fructose were measured for each stage of ovule development, both for sexual and apomictic plants. The enzymes were localised by immunohistochemistry with heterologous antibodies. A distinct difference between sexual and apomictic plants was observed in the localisation of sucrose synthase activity as well as in the amount of activity, especially in the early stages of ovular development. Invertase activity localisation was comparable between ovules of the sexual and apomictic plants, but its activity is clearly higher in ovules of sexual plants. The localisation of the enzymes coincided with the place of activity. For both sexual and apomictic plants the amount of sucrose in the ovaries increased with the stage of ovule development. Differences in the amount of sucrose between sexual and apomictic plants in ovaries with ovules in comparable stages of development were detected. A delay in the onset of carbohydrate metabolism during early stages of ovule development characterises the apomictic plant.Abbreviations MMC megaspore mother cell - MC meiocyte - MS megaspore - AI apospore initial - CO coenocyte - MES mature embryo sac - SuSy sucrose synthase - INV invertase - BMM buthylmethyl methacrylate - DTT dithiothreitol - DAPI 4,6-diamidino-2-phenylindole - PBS phosphate-buffered saline     

A study of chromium in human cataractous lenses and whole blood of diabetics,senile, and normal population

Chromium (Cr) is of known biological importance, necessary for the maintenance of normal glucose metabolism. There is a lower level of blood Cr concentrations in cases of diabetes. Diabetes carries a risk of cataract development, so the potential effects of Cr on the eye may need to be studied in more depth. The presence of this trace element in both normal and cataractous human lenses has to our knowledge not been investigated so far. The concentration of total Cr in 61 human lenses and 38 blood samples was determined by electrothermal atomic absorption spectrometry with Zeeman effect (EAASZ). Analysis of the levels of Cr in human lenses shows a significant difference between normal and diabetic populations, and an absence of difference between senile and diabetic populations.     

Zinc kinetics in insulin-dependent diabetes mellitus patients

Zinc has an important role in the control of carbohydrate metabolism, and diabetic patients are at risk for zinc deficiency. However, there are conflicting data concerning nutritional zinc status. In order to investigate this topic, 10 normal and 10 insulin-dependent diabetic patients were studied following venous zinc tolerance test. Our results found no evidence of zinc deficiency or of changes on the kinetic parameters of zinc in patients with insulin-dependent diabetes mellitus following a venous zinc tolerance test.     

Development of imaginal competence to adipokinetic hormone in Locusta: lipid and carbohydrate levels, and glycogen phosphorylase activity in precocene-induced adultiforms

Abstract. Adipokinetic responses to injection of synthetic adipokinetic hormone I (sAKH) were investigated in precocene-induced fifth-instar adultiforms and in chemically allatectomized but morphogenetically normal adults of Locusta migratoria (L.). The results were compared with data on normal fifth (=last)-instar nymphs and normal adults. Chemical allatectomy did not affect the resting level of lipid in the haemolymph, nor the slight decrease of haemolymph carbohydrate concentration induced by sAKH. The effects of chemical allatectomy on sAKH-induced hyperlipaemia, the resting level of haemolymph carbohydrate, total glycogen phosphorylase specific activity, as well as sAKH-induced phosphorylase activation in the fat body, were mostly minor and probably indirect. The concentrations of lipid and carbohydrate in the haemolymph, and sAKH-induced activation of fat body glycogen phosphorylase were more or less similar in normal fifth-instar nymphs, normal adults and fifth-instar adultiforms. Thus, precocious metamorphosis did not affect markedly those parameters which show no or slight changes during normal metamorphosis. In contrast, parameters which change substantially during normal metamorphosis (sAKH-induced hyperlipaemia, sAKH-induced changes in haemolymph carbohydrate level and total glycogen phosphorylase activity) showed similar changes in the course of precocious metamorphosis; the values for fifth-instar adultiforms were similar to those obtained for normal adults, but differed markedly from those found in normal fifth-instar nymphs. Thus, accelerated (precocious) morphological adult development is strongly correlated with accelerated imaginal target competence to AKH and with relevant physiological development.     

Regulation of rat hepatic stearoyl coenzyme A desaturase. The roles of insulin and carbohydrate.

The rat hepatic stearoyl-CoA desaturation decreased by 3.7-fold in streptozotocin-induced diabetes. Insulin treatment of diabetic rats increased the enzyme activity by 7-fold. In marked contrast to glucose administration, fructose feeding in diabetic rats resulted in 20-fold stimulation of stearoyl-CoA desaturation, although both carbohydrates stimulated stearoyl-CoA desaturation in normal rats. Measurement of the microsomal electron transfer components showed no significant changes in the NADH-cytochrome b5 reductase activity or in the concentration of cytochrome b5. However, the activity of the terminal desaturase changed in a parallel fashion as the amount of terminal desaturase reflect changes in the overall desaturation. Supplementation of various microsomes with the saturating amount of purified terminal desaturase resulted in the formation of similar amounts of catalytically active complex and increased the stearoyl-CoA desaturation to the same level suggesting that the changes in the amount of terminal desaturase reflect changes in the overall desaturation. The results support the suggestion that both insulin and the intermediates of carbohydrate metabolism are involved in the regulation of terminal desaturase.     

Ameliorative property of Sesbania grandiflora on carbohydrate metabolic enzymes in the liver and kidney of streptozotocin-induced diabetic rats

In diabetic condition, endogenous glucose synthesis will be elevated due to defect in the action of vital enzymes involved in carbohydrate metabolism, which is the main cause for hyperglycemia. The current study was designed to explore the anti-hyperglycemic efficacy of Sesbania grandiflora flower (SGF) extract by evaluating the concentration of C-peptide, insulin, glucose, glycosylated hemoglobin (HbA_1C), hemoglobin (Hb), glycogen and carbohydrate metabolic enzymes activities in diabetic rats. The study found to lower the level of glucose, HbA_1C and simultaneously ameliorated concentrations of C-peptide, insulin, hemoglobin (Hb), glycogen and carbohydrate metabolic enzymes activities in SGF treated (250 mg/kg body weight for 45 days) diabetic rats. Moreover, SGF administered diabetic rats showed diminished consumption of food and water at the same time improved body weight. The results obtained from the present study were compared with glibenclamide treated (600 µg/kg body weight) diabetic rats. SGF were supplemented to normal rats to rule out toxic effect of SGF, to explore any significant alteration in the above parameters. Hence, the results depict that SGF modulated the carbohydrate metabolic enzymes activities through ameliorating the secretion of insulin and diminishing the level of glucose concentration in STZ-induced diabetic rats by its bioactive compounds.     

Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing

The skin cells chiefly depend on carbohydrate metabolism for their energy requirement during cutaneous wound healing. Since the glucose metabolism is greatly hampered in diabetes and this might affect wound repair process. This prompted us to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the wound tissues of normal and streptozotocin-induced diabetic rats following excision-type of cutaneous injury. The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding. Interestingly, a significant alteration in all these enzyme activities was observed in diabetic rats. The activity of PFK was increased but HK, LDH and CS showed a decreased activity in the wound tissue of diabetics as compared to normal rats. However G6PD exhibited an elevated activity only at early stage of healing in diabetic rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the wound tissue of diabetic rats may affect the energy availability for cellular activity needed for repair process and this may perhaps be one of the factor responsible for impaired healing in these subjects. (Mol Cell Biochem 270: 71–77, 2005)     

Effect of tangeretin,a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats

The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide – a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential.     

Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non-diabetic rats

Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss-Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease.     

微量元素对糖尿病大鼠糖脂代谢的影响

目的观察微量元素铬对糖尿病大鼠糖脂代谢的影响。方法选糖尿病大鼠经灌胃给予有机铬水溶液治疗12周后,分别观察口服有机铬200μg/d及400μg/d的糖尿病大鼠空腹血糖及血脂水平(血清总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白)。实验分为4组:1组为正常对照组;2组为铬200μg/d组;3组为铬400μg/d组;4组为糖尿病对照组。结果有机铬具有明显降低血糖、血清总胆固醇、低密度脂蛋白和甘油三酯及升高高密度脂蛋白的作用(P0.05~P0.01)。结论有机铬能明显改善糖尿病大鼠的糖脂代谢。