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.     

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.     

Mechanisms of antihyperglycemic effect of p-methoxycinnamic acid in normal and streptozotocin-induced diabetic rats

We investigated the antihyperglycemic effect of p-methoxycinnamic acid (p-MCA), a cinnamic acid derivative, on plasma glucose and insulin concentrations, activities of hepatic glucose-regulating enzymes and hepatic glycogen content in normal and streptozotocin (STZ)-induced diabetic rats. p-MCA (10-100 mg/kg, PO) dose-dependently decreased plasma glucose concentration in both normal and diabetic rats in the oral glucose tolerance test. To investigate the chronic effects of p-MCA on glucose metabolism, p-MCA (40 mg/kg, PO) was administered to normal and diabetic rats once a day for 4 weeks. p-MCA reduced plasma glucose concentration in diabetic rats, which was observed during the 4-week study. However, p-MCA treatment did not change plasma glucose concentrations in normal rats during the 4-week study. p-MCA also reduced the excessive activities of hepatic glucose-6-phosphatase, hepatic hexokinase, glucokinase and phosphofructokinase in diabetic rats and increased hepatic glycogen in these rats. In p-MCA-treated normal rats, there were no changes in the activities of hepatic glucose-regulating enzymes, hepatic glycogen and glucose-6-phosphate. Our findings suggested that p-MCA exert its antihyperglycemic effect by increasing insulin secretion and glycolysis, and by decreasing gluconeogenesis.     

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.     

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.     

Effect of Rebaudioside A, a diterpenoid on glucose homeostasis in STZ-induced diabetic rats

Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (P<0.05) increase in the levels of plasma glucose and glycosylated hemoglobin and significant (P<0.05) decrease in the levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly (P<0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were significantly (P<0.05) decreased in the liver along with glycogen. Oral treatment with Reb A to diabetic rats significantly (P<0.05) decreased blood glucose and reversed these hepatic carbohydrate metabolizing enzymes in a significant manner. Histopathology changes of pancreas confirmed the protective effects of Reb A in diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes.     

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.     

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.     

Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice

Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM.     

Plasma glucose-lowering action of Hon-Chi in streptozotocin-induced diabetic rats.

Hon-Chi was used for anti-hyperglycemic activity screening in streptozotocin-induced diabetic rats (STZ-diabetic rats) in an attempt to develop new substances for handling diabetes. Mandarin Hon-Chi is red yeast rice fermented with Monascus pilous and Monascus purpureus. Single oral administration of Hon-Chi decreased plasma glucose in STZ-diabetic rats in a dose-dependent manner from 50 mg/kg to 350 mg/kg. Similar treatment with Hon-Chi also lowered the plasma glucose in normal rats as effectively as that produced in STZ-diabetic rats. In addition, oral administration of Hon-Chi at the highest dose (350 mg/kg) attenuated the elevation of plasma glucose induced by an intravenous glucose challenge test in normal rats. Moreover, mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were reversed in a dose-dependent manner by the repeated oral treatment of Hon-Chi three times daily for two weeks. Otherwise, hyperphagia in STZ-diabetic rats was markedly reversed by similar repeated treatment of Hon-Chi. The obtained results suggest that oral administration of Hon-Chi could decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin.     

Cinnamaldehyde—A potential antidiabetic agent

Cinnamonum zeylanicum (cinnamon) is widely used in traditional system of medicine to treat diabetes in India. The present study was carried out to isolate and identify the putative antidiabetic compounds based on bioassay-guided fractionation; the compound identified decreased the plasma glucose levels. The active compound was purified by repeat column and structure of cinnamaldehyde was determined on the basis of chemical and physiochemical evidence. The LD(50) value of cinnamaldehyde was determined as 1850+/-37 mg/kg bw. Cinnamaldehyde was administered at different doses (5, 10 and 20 mg/kg bw) for 45 days to streptozotocin (STZ) (60 mg/kg bw)-induced male diabetic wistar rats. It was found that plasma glucose concentration was significantly (p<0.05) decreased in a dose-dependent manner (63.29%) compared to the control. In addition, oral administration of cinnamaldehyde (20 mg/kg bw) significantly decreased glycosylated hemoglobin (HbA(1C)), serum total cholesterol, triglyceride levels and at the same time markedly increased plasma insulin, hepatic glycogen and high-density lipoprotein-cholesterol levels. Also cinnamaldehyde restored the altered plasma enzyme (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase) levels to near normal. Administration of glibenclamide, a reference drug (0.6 mg/kg bw) also produced a significant (p<0.05) reduction in blood glucose concentration in STZ-induced diabetic rats. The results of this experimental study indicate that cinnamaldehyde possesses hypoglycemic and hypolipidemic effects in STZ-induced diabetic rats.     

Insulin secretagogue effect of Ichnocarpus frutescence leaf extract in experimental diabetes: a dose-dependent study

Ichnocarpus frutescence (L.) R.Br. is an evergreen plant and many preparations have been used in traditional Indian medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. In the present study we prepared various extracts of I. frutescence (IF) leaves which were tested against streptozotocin-induced diabetic rats. IF leaf methanolic extract (IFLMExt) showed significant plasma glucose lowering effect. Therefore, we prepared IFLMExt, which was tested against different types of glycemia (normal, glucose-fed hyperglycemic and streptozotocin-induced diabetic rats) for their potential to induce insulin secretion and cellular insulin responses. Fasting plasma glucose (FPG) levels were determined at different doses and times following treatment with IFLMExt or with vehicle in normal, glucose fed-hyperglycemic and diabetic rats. Oral administration of IFLMExt led to a significant blood glucose-lowering effect in glucose-fed hyperglycemic and diabetic rats. The hypoglycemic effect was observed at doses of 100 and 200 mg/(kg bw) after 6 and 2 h administration, respectively, in glucose-fed hyperglycemic rats. The maximum effect of IFLMExt was detected at 2 h with 200 mg/(kg bw) in diabetic animals and this profile was maintained for the next 6 h (37.23%) but increased after that at 24 h. Oral administration of IFLMExt daily for 45 days to diabetic rats significantly reduced the FPG (54.5%) to near normal. After 7 days of streptozotocin administration plasma insulin decreased in diabetic controls compared to normal controls. Treatment with IFLMExt significantly prevented the decrease in plasma insulin levels from day 0 to 45 in comparison to diabetic controls. Oral administration of n-hexane fraction led to a significant glucose-lowering effect in diabetic rats (54.50%). Histopathological examination showed that IFLMExt extract protected the pancreatic tissue from streptozotocin-induced damage enormously. Oral administration of IFLMExt extract and n-hexane fraction to normal and streptozotocin-induced diabetic rats decreased plasma glucose levels without hypoglycemic effect. The results suggest that methanolic extract and n-hexane fraction of IF may provide new therapeutic avenues against diabetes.     

Insulin-like effect of vanadate on malic enzyme and glucose-6-phosphate dehydrogenase activities in streptozotocin-induced diabetic rat liver

The effect of oral administration of sodium orthovanadate on hepatic malic enzyme (EC 1.1.1.40) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) activities was investigated in nondiabetic and diabetic rats. Streptozotocin-induced diabetic rats were characterized by 4.7-fold increase in plasma glucose and 82% decrease in plasma insulin levels. The activities of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were also diminished (P less than 0.001). Vanadate treatment in diabetic rats led to a significant decrease (P less than 0.001) in plasma glucose levels and to the normalization of enzyme activities, but it did not alter plasma insulin levels. In nondiabetic rats vanadate decreased the plasma insulin level by 64% without altering the enzyme activities. Significant correlation was observed between plasma insulin and hepatic lipogenic enzyme activities in untreated and vanadate-treated rats. Vanadate administration caused a shift to left in this correlation suggesting improvement in insulin sensitivity.     

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.     

Metformin-like effects of Quei Fu Di Huang Wan, a Chinese herbal mixture, on streptozotocin-induced diabetic rat.

Effect on plasma glucose concentration of Quei Fu Di Huang Wan (Quei Fu DHW), the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine, was investigated in diabetic rats deficient in insulin. Changes of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats) receiving repeated oral administration of Quei Fu DHW were determined. Also, the mRNA level (by Northern blotting) and protein level (by Western blotting) of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were measured to compare differences between groups receiving repeated oral administration of Quei Fu DHW, metformin, and two active herbs (Zou Guei or Fuzei) at effective dosages. In STZ-diabetic rats, acute oral administration of Quei Fu DHW decreased the plasma glucose level significantly in a dose-dependent manner from 5 mg/kg to 26.0 mg/kg. Similar treatment with Quei Fu DHW also brought on a plasma glucose-lowering effect in normal rats, although the effectiveness was not as significant as in STZ-diabetic rats. Repeated oral treatment of Quei Fu DHW at 26 mg/kg every 8 h, three times daily for 3 days, produced a plasma glucose-lowering activity similar to that of metformin-treatment in STZ-diabetic rats. Oral administration of Zou Guei (Cinnamomi Cortex) or Fuzei (Aconiti Tuber), the individual constituent of Quei Fu DHW, at the dose of 50 mg/kg into STZ-diabetic rats for 3 days normalized hyperglycemia. Similar to the repeated treatment with Quei Fu DHW, Fuzei at the effective dose reversed the elevated mRNA and protein levels of PEPCK in liver from STZ-diabetic rats. This is consistent with findings that metformin restored the increased gene expression of PEPCK in liver from STZ-diabetic rats. However, the gene expression of PEPCK in STZ-diabetic rats was not influenced by similar treatment with Zou Guei. The present study found that oral administration of Quei Fu DHW could decrease hepatic gluconeogenesis in a way similar to metformin in lowering plasma glucose in diabetic rats lacking insulin. Thus, this preparation may be a helpful adjuvant for the treatment of diabetic disorders in clinical practice.     

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.     

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.     

Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.

The intake of dietary fructose has undergone a marked increase around the world, especially the developed countries, in recent times. Stevioside, a glycoside contained in the leaves of Stevia rebaudiana Bertoni (Compositae), was used to screen the effect induced by a diet containing 60% fructose on insulin resistance in rats. Single oral administration of stevioside for 90 min decreased plasma glucose concentrations in a dose-dependent manner in rats receiving fructose-rich chow for four weeks. In addition, insulin action on glucose disposal rate was measured using the glucose-insulin index, the product of the areas under the curve of glucose, and insulin during the intraperitoneal glucose tolerance test. Oral administration of stevioside (5.0 mg/kg) in rats given four weeks of fructose-rich chow for 90 min reversed the value of glucose-insulin index, indicating that stevioside has the ability to improve insulin sensitivity in this insulin-resistant animal model. Time for the loss of plasma glucose lowering response to tolbutamide (10.0 mg/kg, i. p.) in fructose-rich chow fed rats was also markedly delayed by repeated stevioside treatment three times daily compared to the vehicle-treated group. The plasma glucose-lowering activity of tolbutamide was introduced to account for varying levels of endogenous insulin secretion, and is widely used as the indicator of insulin resistance development. Thus, it provided the supportive data that repeated oral administration of stevioside delayed the development of insulin resistance in rats on a high-fructose diet. Increased insulin sensitivity by stevioside administration was further identified using the plasma glucose-lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral administration of stevioside at 0.2 mg/kg three times daily into STZ-diabetic rats for ten days increased the response to exogenous insulin. Taken together, this demonstrated that oral administration of stevioside improves insulin sensitivity, and seems suitable as an adjuvant for diabetic patients and/or those that consume large amounts of fructose.     

Central adrenergic suppression augments the insulin and glucagon secretory, and the glycogenolytic responses in streptozotocin-diabetic rats.

It has been suggested that the increased activity of the sympathetic nervous system and the resultant increase in the tissue catecholamine levels contribute to the pathogenesis of diabetes. In this study we evaluated the effect of clonidine, a central adrenergic agonist that decreases sympathetic tone, on the serum levels of glucose, insulin, glucagon and norepinephrine and on the hepatic glycogen content in normal and streptozotocin-diabetic rats. The animals were treated with clonidine 25 micrograms/kg/day interperitoneally for 3 weeks to suppress the central adrenergic impulses. Clonidine treatment significantly increased the weight gain, but did not affect plasma glucose, insulin, glucagon and norepinephrine in the diabetic animals. Pancreatic insulin and liver glycogen contents were significantly higher in the clonidine-treated than in the untreated diabetic rats. However, clonidine did not affect pancreatic insulin and liver glycogen content of nondiabetic animals. The intravenous administration of glucagon increased plasma glucose in the clonidine-treated, but not in the saline-treated diabetic rats. Insulin-induced hypoglycemia significantly enhanced glucagon release in clonidine-treated but not in saline-treated diabetic rats. We conclude that the suppression of central adrenergic activity may ameliorate the effects of insulin insufficiency on pancreatic hormone secretion and hepatic glycogen content.     

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.