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.     

Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats

Epidemiological studies have demonstrated that diabetes mellitus is a serious health burden for both governments and healthcare providers. This study was hypothesized to evaluate the antihyperglycemic potential of eugenol by determine the activities of key enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for 30 days. The dose 10 mg/kg b.w. significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats were significantly reverted to near normal levels by the administration of eugenol. Further, eugenol administration to diabetic rats improved body weight and hepatic glycogen content demonstrated the antihyperglycemic potential of eugenol in diabetic rats. The present findings suggest that eugenol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to alleviate the adverse effects of diabetes.     

Galangin,a natural flavonoid reduces mitochondrial oxidative damage in streptozotocin-induced diabetic rats

Objective: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats.

Methods: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40?mg?kg^?1 body weight (BW)). Galangin (8?mg?kg^?1 BW) or glibenclamide (600?µg?kg^?1 BW) was given orally daily once for 45 days to both healthy and diabetic rats.

Results: Diabetic rats showed significant (P?P?P?P?P?Conclusion: From the results, we conclude that galangin could maintain liver mitochondrial function in diabetic rats.     

Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Epidemiological studies have demonstrated that the diabetes mellitus is a serious health burden for both governments and healthcare providers. The present study was hypothesized to evaluate the antihyperglycemic potential of fraxetin by determining the activities of key enzymes of carbohydrate metabolism in streptozotocin (STZ) – induced diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg b.w). Fraxetin was administered to diabetic rats intra gastrically at 20, 40, 80 mg/kg b.w for 30 days. The dose 80 mg/kg b.w, significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as glucokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and hepatic enzymes (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP)) in the liver tissues of diabetic rats were significantly reverted to near normal levels by the administration of fraxetin. Further, fraxetin administration to diabetic rats improved body weight and hepatic glycogen content demonstrated its antihyperglycemic potential. The present findings suggest that fraxetin may be useful in the treatment of diabetes even though clinical studies to evaluate this possibility may be warranted.     

Efficacy of coumarin on hepatic key enzymes of glucose metabolism in chemical induced type 2 diabetic rats

The study was undertaken to evaluate the antidiabetic effect of coumarin on carbohydrate metabolic key enzymes in control and streptozotocin (STZ)-nicotinamide (NA)-induced diabetic rats. On oral administration of coumarin at a dose of 100 mg/kg body weight per day to diabetic rats for 45 days; resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA₁c) and increase in the levels of insulin and hemoglobin. Administration of coumarin caused a significant increase in the levels of glycolytic enzyme (hexokinase) and hepatic shunt enzyme (glucose-6-phophate dehydrogenase) whereas significant decrease in the levels of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in diabetic treated rats. Furthermore, protection against body weight loss of diabetic animals also observed. This study indicates that the administration of coumarin to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels.     

Therapeutic Potential of Clove Essential Oil in Diabetes: Modulation of Pro-Inflammatory Mediators,Oxidative Stress and Metabolic Enzyme Activities

Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic β cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC₅₀=298.0±2.75 μg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.     

Effect of sakuranin on carbohydrate-metabolizing enzyme activity modifications in streptozotocin-nicotinamide-induced diabetic wistar rats

This study is to assess the glucose lowering activity of sakuranin in diabetes induced rats by streptozotocin (STZ) and nicotinamide (NA). Diabetic rats were treated sakuranin for 45 days (20, 40, 80 mg/kg) by orally. Sakuranin (80 mg/kg body weight) was normalized the changes of abnormal blood glucose plasma glucose and plasma insulin levels. Hence, we have continued the further research with this active dose of 80 mg/kg sakuranin. The plasma glucose and glycosylated hemoglobin (HbA₁c) reduced and insulin, glycogen and hemoglobin levels increased by Sakuranin administration in diabetic rats. Additionally, hexokinase and glucose-6-phophate dehydrogenase activities increased and glucose-6-phosphatase and fructose-1,6-bisphosphatase activities decreased in diabetic condition while administration of treated compound. In this observed result signified that sakuranin may have potential role of diabetic condition rats by evidenced with reducing glucose and increasing insulin and also protect the carbohydrate metabolic changes.     

Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic,gluconeogenic and lipogenic enzymes

Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADPlinked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4fold higher blood glucose level and a 0.7fold lower body weight compared to normal controls. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities of gluconeogenic enzymes were higher in both liver and kidney during diabetes, however the activities of the lipogenic enzymes were decreased in both tissues during diabetes. Trigonella seed powder treatment to diabetic rats for 21 days brought down the elevated fasting blood glucose levels to control levels. The altered enzyme activities were significantly restored to control values in both the liver and kidney after Trigonella seed powder treatment. The therapeutic role of Trigonella seed powder in type1 diabetes as exemplified in this study can be attributed to the change of glucose and lipid metabolising enzyme activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney. These biochemical effects exerted by Trigonella seeds make it a possible new therapeutic in type1 diabetes.     

Effect of S-allylcysteine,a sulphur containing amino acid on iron metabolism in streptozotocin induced diabetic rats

It is suggested that iron may play a role in the pathogenesis of diabetes. Iron is not only chaperoned through its essential functional pathways, but it also causes damage to biological systems by catalyzing the production of reactive oxygen species. So, the parenchymal tissues of several organs are subject to cell injury and functional insufficiency due to excess deposition of iron. The present study investigated the effects of S-allylcysteine (SAC), a sulphur containing amino acid derived from garlic on the changes in iron metabolism induced by oxidative stress in tissues, as well as on serum biochemical parameters of streptozotocin (STZ)-induced diabetic rats. SAC was administered orally for 45 days to control and experimental diabetic rats. The effects of SAC on glucose, insulin, serum iron, ferritin, transferrin, serum bilirubin, heart heme oxygenase activity (HO) and δ-aminolevulinicacid dehydratase activity (δ-ALA-D) in liver and kidneys were studied. The levels of glucose, iron, ferritin, bilirubin and HO in liver were increased significantly (p < 0.05) whereas the levels of insulin, transferrin and δ-ALA-D in tissues were decreased in diabetic rats. Administration of SAC to diabetic rats showed a decrease in blood glucose, iron, ferritin, bilirubin and HO. In addition, the levels of insulin, transferrin and δ-ALA-D activity in tissues were increased in SAC treated diabetic rats. These findings suggest that S-allylcysteine could have a protective effect against alterations in oxidative stress induced iron metabolism in the diabetic state which was evidenced by the capacity of this natural antioxidant to modulate parameters of iron metabolism.     

Effects of sodium-orthovanadate and<Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes

Sodium-orthovanadate (SOV) and seed powder ofTrigonella foenum graecum Linn. (common name: fenugreek, family: Fabaceae) (TSP) besides being potential hypoglycemic agents have also been shown to ameliorate altered lipid metabolism during diabetes. This study evaluates the short-term effect of oral administration of SOV and TSP separately and in concert (for 21 days) on total lipid profile and lipogenic enzymes in tissues of alloxan diabetic rats. Diabetic rats showed 4-fold increase in blood glucose. The level of total lipids, triglycerides and total cholesterol in blood serum increased significantly during diabetes. During diabetes the level of total lipids increased significantly (P < 0001) in liver and in kidney by 48% and 55%, respectively, compared to control. Triglycerides level increased by 32% (P < 001) in liver and by 51% (P < 0005) in kidney, respectively, compared to control. Total cholesterol level also increased significantly in both liver and kidney (P < 0.01 andP < 0001, respectively). The activities of NADP-linked enzymes; namely glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and the activities of lipogenic enzymes namely ATP-citrate lyase ΜTP-CL) and fatty acid synthase (FAS) were decreased significantly in liver and increased in kidney during diabetes as compared to control. SOV and TSP administration to diabetic animals prevented the development of hyperglycemia and alteration in lipid profile in plasma and tissues and maintained it near normal. Maximum prevention was observed in the combined treatment with lower dose of SOV (0.2%) after 21 days. We are presenting for the first time effectiveness of combined treatment of SOV and TSP in amelioration of altered lipid metabolism during experimental type-I diabetes     

Assessment of In Vivo Antidiabetic Properties of Umbelliferone and Lupeol Constituents of Banana (Musa sp. var. Nanjangud Rasa Bale) Flower in Hyperglycaemic Rodent Model

Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana flower is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. This study is based on an investigation of the in vivo antihyperglycaemic activity of Umbelliferone (C1) and Lupeol (C2) isolated from the ethanol extract of banana flower (EF) in alloxan induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EF (100 and 200 mg/kg b. wt.) for 4 weeks showed deterioration in fasting hyperglycaemia and reversal of abnormalities in serum/urine protein, urea and creatinine, when compared to the diabetic control group of rats. The diabetic group of rats fed with EF, C1 and C2 (100 mg/kg b. wt.) once daily, for a period of 28 days resulted in a significant reduction of diabetic symptoms viz., polyphagia, polydipsia, polyuria and urine sugar together with an improved body weight. HbA1c extent was reduced whereas levels of insulin and Hb were increased. Both the extract and compounds wielded positive impacts in diabetic rats by reversal of altered activities of hepatic marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose-6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase, lactate dehydrogenase) and pyruvate kinase. The characteristic diabetic complications such as hypercholesterolemia and hypertriacylglycerolemia also significantly reverted to normal in the serum/liver of diabetic rats. Besides these, the treatment increased the activities of enzymatic and non-enzymatic antioxidants in the serum and liver. The histological observations revealed a marked regeneration of the β-cells in the drug treated diabetic rats. In conclusion, the present study illustrates that EF, C1 and C2 enhances the glycolytic activities, besides increasing the hepatic glucose utilization in diabetic rats by stimulating insulin secretion from the remnant β-cells along with potential enzymatic and non-enzymatic antioxidant activities.     

Testicular oxidative damage and role of combined antioxidant supplementation in experimental diabetic rats

The present study was designated to assess oxidative damage and its effect on germ cell apoptosis in testes of streptozotocin (STZ)-induced diabetic rats. The role of antioxidant supplementation with a mixture of vitamins E and C and alpha lipoic acid for protection against such damage was also evaluated. Forty-five adult male rats were randomly divided into three groups: group I, control, non-diabetic rats; group II, STZ-induced, untreated diabetic rats; group III, STZ-induced diabetic rats supplemented with a mixture of vitamins E and C and alpha lipoic acid. Glycated hemoglobin (HbA_1C), glucose, and insulin levels were estimated in blood samples. Malondialdehyde (MDA), the activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and caspase-3 in addition to testosterone (T) level were all determined in testicular tissues. Histopathological studies using H&E stain, as well as, immunohistochemical detection of apoptosis using (TUNEL) method were also performed. Blood glucose and HbA_1c were significantly increased while insulin was significantly decreased in STZ-induced diabetic rats as compared with controls. In rat testicular tissues, MDA, and caspase-3 activity were significantly elevated while SOD and GPx enzymatic activities as well as T level were significantly decreased in diabetic rats as compared with control group. Antioxidant supplementation to diabetic rats restored the testicular enzymatic activities of SOD and GPx to almost control levels, in addition, MDA and caspase-3 activity decrease while T increase significantly as compared with untreated diabetic group. Prominent reduction of germ cell apoptosis was found in diabetic rats supplemented with antioxidants. An important role of testicular oxidative damage and germ cell apoptosis in diabetes-induced infertility could be suggested, treatment with antioxidants has a protective effect by restoring SOD and GPx antioxidant enzymatic activity.     

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.     

Antihyperglycemic and antioxidant effects of a flavanone, naringenin, in streptozotocin–nicotinamide-induced experimental diabetic rats

In the present study, the putative antihyperglycemic and antioxidant effects of a flavanone, naringenin, were evaluated in comparison with those of glyclazide, a standard drug for therapy of diabetes mellitus. Diabetes was induced experimentally in 12-h-fasted rats by intraperitoneal injections of first streptozotocin (50 mg/kg b.w.) and then of nicotinamide (110 mg/kg b.w.) after a 15-min interval. Untreated diabetic rats revealed the following in comparison with normal rats: significantly higher mean levels of blood glucose and glycosylated hemoglobin, significantly lower mean levels of serum insulin, significantly lower mean activities of pancreatic antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase), significantly lower mean levels of plasma non-enzymatic antioxidants (reduced glutathione, vitamin C , vitamin E), significantly elevated mean levels of pancreatic malondialdehyde (MDA) and significantly elevated mean activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Following oral administration of naringenin (50 mg/kg b.w./day) to diabetic rats for 21 days, the following observations were made in comparison with untreated diabetic rats: significantly lower mean levels of fasting blood glucose and glycosylated hemoglobin, significantly elevated serum insulin levels, significantly higher mean activities of pancreatic enzymatic antioxidants, significantly higher mean levels of plasma non-enzymatic antioxidants, lower mean pancreatic tissue levels of MDA and lower mean activities of ALT, AST, ALP and LDH in serum. The values obtained in the naringenin-treated animals approximated those observed in glyclazide-treated animals. Histopathological studies appeared to suggest a protective effect of naringenin on the pancreatic tissue in diabetic rats. These results suggest that naringenin exhibits antihyperglycemic and antioxidant effects in experimental diabetic rats.     

Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.     

Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan-induced diabetic rats

We evaluated the effect of sodium molybdate on carbohydrate metabolizing enzymes and mitochondrial enzymes in diabetic rats. Diabetic rats showed a significant reduction in the activities of glucose metabolising enzymes like hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and in the level of glycogen. An elevation in the activities of aldolase, glucose-6-phosphatase, fructose 1,6- bisphosphatase, glycogen phosphorylase and in the level of blood glucose were also observed in diabetic rats when compared to control rats. The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome-C-oxidase were also significantly lowered in diabetic rats. Molybdate administration to diabetic rats reversed the above changes in a significant manner. From our observations, we conclude that administration of sodium molybdate regulated the blood sugar levels in alloxan-induced diabetic rats. Sodium molybdate therapy not only maintained the blood glucose homeostasis but also altered the activities of carbohydrate metabolising enzymes. Molybdate therapy also considerably improved the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.     

Ameliorative effect of kaempferol,a flavonoid,on oxidative stress in streptozotocin-induced diabetic rats

Abstract

Objective

The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats.

Methods

Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats.

Results

The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal.

Conclusion

The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.     

Diabetes and mitochondrial bioenergetics: alterations with age

Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, some of the results reported are controversial, since experimental conditions, such as aging, and/or strain of animals used were different. The purpose of this study was to evaluate the metabolic changes in liver mitochondria, both in the presence of severe hyperglycaemia (STZ-treated rats) and mild hyperglycaemia (Goto-Kakizaki (GK) rats). Moreover, metabolic alterations were evaluated both at initial and at advanced states of the disease. We observed that both models of type 1 and type 2 diabetes presented alterations on respiratory chain activity. Because of continual severe hyperglycaemia, 9 weeks after the induction of diabetes, the respiratory function declined in STZ-treated rats, as observed by membrane potential and respiratory ratios (RCR, P/O, and FCCP-stimulated respiration) assessment. In contrast, GK rats of 6 months age presented increased respiratory ratios. To localize which respiratory complexes are affected by diabetes, enzymatic respiratory chain activities were evaluated. We observed that succinate dehydrogenase and cytochrome c oxidase activities were significantly augmented both in STZ-treated rats and GK rats of 6 months age. Moreover, H(+)-ATPase activity was also significantly increased in STZ-treated rats with 3 weeks of diabetes and in GK rats of 6 months age as compared to controls. Therefore, these results clearly suggest that both animal models of diabetes present some metabolic adjustments in order to circumvent the deleterious effects promoted by the high glucose levels typical of the disease.     

Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination withTrigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual signs of cataract. Alterations in the activities of glucose metabolizing enzymes (hexokinase, aldose reductase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase) and antioxidant enzymes (glutathione peroxidase, glutathione reductase) besides the levels of related metabolites, [sorbitol, fructose, glucose, thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH)]were observed in the lenses from diabetic rats and diabetic rats treated with insulin (2 IU/day), SOV (0.6 mg/ml),T. f. graecum seed powder (TSP, 5%) and TSP (5%) in combination with lowered dose of vanadium SOV (0.2 mg/ml), for a period of 3 weeks. The activity of the enzymes, hexokinase, aldose reductase and sorbitol dehydrogenase was significantly increased whereas the activity of glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase decreased significantly in lenses from 3 week diabetic rats. Significant increase in accumulation of metabolites, sorbitol, fructose, glucose was found in diabetic lenses. TBARS measure of peroxidation increased whereas the levels of antioxidant GSH decreased significantly in diabetic condition. Insulin restored the levels of altered enzyme activities and metabolites almost to control levels. Sodium orthovanadate (0.6 mg/ml) andTrigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination withTrigonella was found to be the most effective in restoring the altered lens metabolism and morphological appearance in diabetes. It may be concluded that vanadate at lowered doses administered in combination withTrigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses, these being significant factors involved in the development of diabetic complications, that reflects in the reduced lens opacity