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.     

Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms

Diabetic patients are at increased risk to develop cognitive deficit and senile dementia. This study was planned to assess the benefits of chronic carnosine administration on prevention of learning and memory deterioration in streptozotocin (STZ)-diabetic rats and to explore some of the involved mechanisms. Rats were divided into 5 groups: i.e., control, carnosine100-treated control, diabetic, and carnosine-treated diabetics (50 and 100 mg/kg). Carnosine was injected i.p. at doses of 50 or 100 mg/kg for 7 weeks, started 1 week after induction of diabetes using streptozotocin. Treatment of diabetic rats with carnosine at a dose of 100 mg/kg at the end of the study lowered serum glucose, improved spatial recognition memory in Y maze, improved retention and recall in elevated plus maze, and prevented reduction of step-through latency in passive avoidance task. Furthermore, carnosine at a dose of 100 mg/kg reduced hippocampal acetylcholinesterase (AChE) activity, lowered lipid peroxidation, and improved superoxide dismutase (SOD) activity and non-enzymatic antioxidant defense element glutathione (GSH), but not activity of catalase. Meanwhile, hippocampal level of nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNF-α), and glial fibrillary acidic protein (GFAP) decreased and level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) increased upon treatment of diabetic group with carnosine at a dose of 100 mg/kg. Taken together, chronic carnosine treatment could ameliorate learning and memory disturbances in STZ-diabetic rats through intonation of NF-κB/Nrf2/HO-1 signaling cascade, attenuation of astrogliosis, possible improvement of cholinergic function, and amelioration of oxidative stress and neuroinflammation.     

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.     

Efficacy of 20-OH-ecdysone on hepatic key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats

The aim of the present investigation was to evaluate the anti-diabetic activity of 20-OH-ecdysone on glucose metabolic key enzymes in control and streptozotocin induced diabetic rats. On oral administration of 20-OH-ecdysone at a dose of 5mg/kg body weight per day to diabetic rats for 30 days resulted in a significant decrease in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and an increase in the levels of insulin and hemoglobin. Administration of 20-OH-ecdysone showed significant increase in the levels of glycolytic enzyme (hexokinase) and hepatic shunt enzyme (glucose-6-phosphate 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 20-OH-ecdysone to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels. A comparison was made between the action of 20-OH-ecdysone and antidiabetic drug-glibenclamide. The effects produced by the 20-OH-ecdysone were comparable to that of glibenclamide.     

Effects of gallic acid on brain lipid peroxide and lipid metabolism in streptozotocin-induced diabetic Wistar rats

This study evaluated the protective effects of gallic acid on brain lipid peroxidation products, antioxidant system, and lipids in streptozotocin-induced type II diabetes mellitus. Streptozotocin-induced diabetic rats showed a significant increase in the levels of blood glucose, brain lipid peroxidation products, and lipids and a significant decrease in the activities of brain enzymic antioxidants. Oral treatment with gallic acid (10 mg and 20 mg/kg) for 21 days significantly decreased the levels of blood glucose, brain lipid peroxidation products, and lipids and significantly increased the activities of brain enzymic antioxidants in diabetic rats. Histopathology of brain confirmed the protective effects of gallic acid. Furthermore, in vitro study revealed the free radical scavenging action of gallic acid. Thus, our study shows the beneficial effects of gallic acid on brain metabolism in streptozotocin-induced type II diabetic rats. A diet containing gallic acid may be beneficial to type II diabetic patients.     

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.     

Augmentation of hepatic and renal oxidative stress and disrupted glucose homeostasis by monocrotophos in streptozotocin-induced diabetic rats

Several recent studies have demonstrated that organophosphorus insecticides (OPI) possess the potential to disrupt glucose homeostasis leading to hyperglycemia in experimental animals. The propensity of OPI to induce hyperglycemia along with oxidative stress may have far-reaching consequences on diabetic outcomes and associated complications. The primary objective of this study was to assess the potential of monocrotophos (MCP), an extensively used OPI, on hepatic and renal oxidative stress markers and dysregulation of hepatic glucose homeostasis in experimentally induced diabetic rats. Rats rendered diabetic by a single dose of streptozotocin (60 mg/kg b.w) were orally administered MCP (0.9 mg/kg b.w/d for 5 d). Monocrotophos per se caused only a marginal increase in blood glucose levels but significantly elevated the blood glucose levels and also disrupted glucose homeostasis by depleting liver glycogen content and increasing the gluconeogenetic enzyme activities in diabetic rats. Experimentally induced diabetes was also associated with alterations in antioxidant enzymes in liver and kidney. MCP markedly enhanced lipid peroxidation in kidney and altered the enzymatic antioxidant defense mechanisms in both liver and kidney of diabetic rats. Collectively our data provides evidence that MCP has the propensity to augment the oxidative stress and further disrupt glucose homeostasis in diabetic rats.     

Intestinal disaccharidases and some renal enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides)

In this study, the effects of bitter yam sapogenin extract or commercial diosgenin on intestinal disaccharidases and some renal enzymes in diabetic rats were investigated. Diabetic male Wistar rats were fed diets supplemented with 1% sapogenin extract or commercial diosgenin for 3 weeks. Plasma glucose, intestinal disaccharidases and the activities of transaminases, acid phosphatase, glucose-6-phosphatase, ATP citrate lyase, glucose-6-phosphate dehydrogenase and pyruvate kinase were assessed for the level of metabolic changes in the kidney of diabetic rats. Sapogenin extract or commercial diosgenin supplementation resulted in a significant decrease in lactase and maltase activities in all three regions of the intestine compared to the diabetic control group. However, the test diets significantly reduced intestinal sucrase activity in the proximal and mid regions. Test diets supplementation resulted in a significant decrease in the activities of the transaminases compared to the normal and diabetic control groups. The activity of glucose-6-phosphatase was significantly increased while the activities of ATP citrate lyase, pyruvate kinase and glucose-6-phosphate dehydrogenase were significantly reduced in the kidney of the diabetic control rats compared to the normal group. Test diets supplementation did not significantly alter glucose-6-phosphatase, ATP citrate lyase and pyruvate kinase activities compared to the diabetic control. However, there was a significant increase in glucose-6-phosphate dehydrogenase activity toward the normal group. In conclusion, the consumption of bitter yam sapogenin extract or commercial diosgenin demonstrated hypoglycemic properties, which are beneficial in diabetes by reducing intestinal disaccharidases activities; however, bitter yam sapogenin extract may adversely affect the integrity of kidney membrane.     

Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic rats

We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa, Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin (STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of glucose oxidation in blood, were also lowered by Rhus verniciflua extract supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts significantly reduced TBARS levels versus diabetic controls. Serum concentrations of liver-function marker enzymes, GOT and GPT, were also restored by Rhus verniciflua (50 mg/kg) supplementation in diabetic rats.     

Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats

Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.     

重构肠道菌群Ⅱ型糖尿病大鼠造模血脂代谢变化及肝细胞线粒体超微结构观察

目的重构肠道菌群Ⅱ型糖尿病大鼠模型脂类代谢变化比较,探讨肠道菌群潜在的调脂作用。方法将64只SD雄性大鼠随机分为对照组、造模组、益生组和去污组。采用高糖高脂喂养,亚致病剂量（30mg／mL）链脲佐菌素腹腔一次性注射造模,分别于2周、4周后取腹腔主动脉血做血脂检测,同时处死大鼠取肝脏做电镜切片观察。结果注射4周后各组出现的胆固醇升高两两比较差异有统计学意义（P〈0．01）,LDL升高差异有统计学意义（P〈0．01）;益生组肝细胞线粒体受损明显;去污组血脂升高相对较轻,肝细胞内有大量脂肪堆积。结论益生菌对Ⅱ型糖尿病大鼠胆固醇升高有一定改善作用,肝线粒体损伤较明显;去污染组损伤相对较轻,而脂肪堆积明显;提示糖尿病脂类代谢与肠道菌群密切相关。     

Protective effects of gallic acid on hepatic lipid peroxide metabolism, glycoprotein components and lipids in streptozotocin-induced type II diabetic Wistar rats

We evaluated the protective effects of gallic acid (3,4,5-trihydroxybenzoic acid) on hepatic lipid peroxidation products, antioxidants, glycoprotein components, and lipids in streptozotocin-induced type II diabetic rats. To induce type II diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg. Gallic acid (10 and 20 mg/kg) treatment was given to diabetic rats orally using an intragastric tube daily for 21 days. Streptozotocin-induced diabetic rats showed a significant increase in the levels of blood glucose, hepatic lipid peroxidation products, glycoprotein components, lipids, and the activity of HMG-CoA reductase and a significant decrease in the levels of plasma insulin and liver glycogen. In addition to this, the activities/levels of hepatic antioxidants were decreased in diabetic rats. Gallic acid (10 and 20 mg/kg) treatment showed significant protective effects on all the biochemical parameters studied in diabetic rats. Thus, our study shows the antihyperglycemic, antilipid peroxidative, antioxidant, and antilipidemic effects of gallic acid in streptozotocin-induced type II diabetic rats. A diet containing gallic acid may be beneficial to type II diabetic patients.     

The effects of streptozotocin-induced diabetes on brucellosis of rats

It is believed that an infection is more common and runs a more protracted course in people with diabetes. In clinical practice, it is important to be aware of these associations, as the prognosis is often dependent upon prompt recognition and appropriate treatment. To show the course of brucellosis in the diabetic state, a model of Brucella melitensis infection was used in the setting of streptozotocin-induced diabetes in rat. B. melitensis infection proceeded more severely in diabetic rats and the severity of diabetes affected the prognosis. However, no association was found between B. melitensis and insulin using in vitro and in vivo experiments. Our study illustrates that B. melitensis infection in diabetes should be taken seriously.     

Enhanced permeability transition explains the reduced calcium uptake in cardiac mitochondria from streptozotocin-induced diabetic rats

Cardiac dysfunction is associated with diabetes. It was previously shown that heart mitochondria from diabetic rats have a reduced calcium accumulation capacity. The objective of this work was to determine whether the reduction in calcium accumulation by cardiac mitochondria from diabetic rats is related to an enhanced susceptibility to induction of the mitochondrial permeability transition. Streptozotocin-induced diabetic rats were used as a model to study the alterations caused by diabetes in the permeability transition, 21 days after streptozotocin administration. Heart mitochondria were isolated to evaluate respiratory parameters and susceptibility to the calcium-dependent permeability transition. Our results show that streptozotocin diabetes facilitates the mitochondrial permeability transition in cardiac mitochondria, resulting in decreased mitochondrial calcium accumulation. We also observed that heart mitochondria from diabetic rats had depressed oxygen consumption during the phosphorylative state. The reduced mitochondrial calcium uptake observed in heart mitochondria from diabetic rats is related to an enhanced susceptibility to the permeability transition rather than to damage to the calcium uptake machinery.     

Changes in key regulatory enzymes of hepatic carbohydrate metabolism after glucose loading of starved rats

When glucose was given to starved rats there was an increase in both 6-phosphofructo 2-kinase and pyruvate kinase activity and a decrease in fructose 2,6-bisphosphatase activity 30 min and 60 min later. These changes were accompanied by an increase in glycogen deposition and by modest, but significant increases in fructose 2,6-bisphosphate levels at the same time. Metabolite measurements indicated that flux through 6-phosphofructo 1-kinase and pyruvate kinase were increased. These results suggest that although glycogen deposition may occur via the gluconeogenic pathway, glycolysis is activated at the same time by changes in the phosphorylation state of key regulatory enzymes as well as by the small rise in fructose 2,6-bisphosphate.     

Insulin replacement therapy in diabetic rats using an osmotic pump normalizes expression of enzymes key to hepatic carbohydrate metabolism.

Intensively treating type I diabetics with continuous subcutaneous insulin infusions or multiple daily insulin injections to normalize mean blood glucose concentrations significantly reduces the onset of secondary diabetic complications when compared to conventionally treated diabetics. Our studies focused on characterizing hepatic enzyme expression in intensively and conventionally treated diabetic rats. Alloxan-induced diabetic rats were conventionally treated with insulin injected twice daily or intensively treated with similar daily dosages of insulin administered via a surgically implanted osmotic pump. Our results demonstrate a significant difference in hepatic enzyme expression when these treatment regimes are compared. In conventionally treated diabetic rats, phosphoenolpyruvate carboxykinase (PEPCK) protein and mRNA levels remained slightly elevated when compared to normal animals, glycogen phosphorylase (GP) protein levels were still slightly decreased, and glycogen synthase (GS) protein and mRNA levels remained at the elevated levels observed in untreated diabetics. In contrast, the protein and mRNA levels of all three enzymes were normalized in the insulin pump-treated animals. These results suggest that intensive insulin therapy improves glycemia directly by normalizing hepatic gene expression while conventional insulin therapy normalizes plasma glucose concentrations indirectly.     

Biotin amelioration of nephrotoxicity in streptozotocin-induced diabetic mice

The current study was carried out to investigate the protective role of biotin in kidney injury and oxidative stress in diabetic mice type 1. Male Swiss albino mice were randomly divided into 3 groups. Control group received saline. Diabetes type 1 was induced in second and third groups by intraperitoneal injection of streptozotocin as a single dose (150 mg/kg). Second group remained as the untreated diabetic group and the third group received 15 mg/kg daily oral dose of biotin for 12 successive days. Biochemical results showed significant elevation in blood glucose and urea levels in both diabetic groups. Also, there is an increase in glomerular areas and decrease in glomerular cellularity in both diabetic groups. Histopathological results showed severe alterations in the untreated diabetic group represented by distorted glomeruli, inflammatory cells, and giant macrophages. In addition, there was an intense immune-reaction response toward acrolein indicator of oxidative damage. Upon biotin administration of diabetic mice, the above mentioned histopathological changes were reduced and also acroline reaction of oxidative damage was diminished. Our findings prove that biotin has a protective role against streptozotocin-induced oxidative damage in kidneys of laboratory mice.     

Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamide-induced diabetic rats

The purpose of this study was to investigate the effect of pterostilbene and its effect on key enzymes of glucose metabolism. Diabetic rats were orally administered with pterostilbene (10, 20, 40 mg/kg) for 2, 4 and 6 weeks on glucose was determined. Administration of pterostilbene at 40 mg/kg significantly decreases plasma glucose. Based on these data, the higher dose, 40 mg/kg pterostilbene, was selected for further evaluation. Oral administration of pterostilbene for 6 weeks on glucose, insulin levels and hepatic enzymes in normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. A significant decrease in glucose and significant increase in plasma insulin levels were observed in normal and diabetic rats treated with pterostilbene. Treatment with pterostilbene resulted in a significant reduction of glycosylated hemoglobin and an increase in total hemoglobin level. The activities of the hepatic enzymes such as hexokinase was significantly increased whereas glucose-6-phosphatase, fructose-1,6-bisphosphatase were significantly decreased by the administration of pterostilbene in diabetic rats. A comparison was made between the action of pterostilbene and the antidiabetic drug--metformin.     

Long-term taurine supplementation reduces mortality rate in streptozotocin-induced diabetic rats

Summary. Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine and vitamin E+selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium supplementations reduce a hard end-point such as mortality due to diabetes. Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%, w/w) or vitamin E (500UI/Kg)+selenium (8mg/Kg) enriched diets. Taurine significantly decreased mortality rate (p<0.04), while vitamin E failed to increase survival. In the late phase of the disease, taurine significantly decreased glycaemia, being vitamin E ineffective. No correlation between glycaemia and survival was found. None of supplementations modified body weight. Thus, only taurine decreases the mortality rate and glycaemia. These results encourage new research in the field, since classical hypoglycaemic agents are unable to decrease mortality in diabetic patients.     

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.