Antidiabetic effect of flax and pumpkin seed mixture powder: effect on hyperlipidemia and antioxidant status in alloxan diabetic rats

Reactive oxygen species play a crucial role in the pathogenesis of diabetes and its complications. This study aims to examine the effects of flax and pumpkin powder seed mixture on alloxan induced diabetes in Wistar rats. Animals were allocated into three groups of six rats each: a control group (CD), diabetic group (DD) and diabetic rats fed with flax and pumpkin seed mixture (DMS) group. The diabetic rats (DD) presented a significant increase in glycemia, plasma and liver lipid parameters such as total lipid, total cholesterol and triglycerides compared to the control group (CD). In addition, plasma and liver malonaldialdehyde levels (MDA, an index of lipid peroxidation) significantly increased compared to (CD). Antioxidant enzymes activities such as catalase, superoxide dismutase, and reduced glutathione (GSH) levels significantly decreased in the plasma and liver of diabetic rats compared to controls. Diet supplemented with flax and pumpkin seed mixture in the DMS group ameliorated antioxidant enzymes activities and level of GSH in diabetic rats and significantly decreased MDA levels. The present study revealed a significant increase in the activities of aspartate aminotransferase and alanine aminotransferase on diabetic status, indicating considerable hepatocellular injury. The administration of flax and pumpkin seed mixture attenuated the increased levels of the plasma enzymes produced by the induction of diabetes and caused a subsequent recovery towards normalization comparable to the control group animals. Our results thus suggest that flax and pumpkin seed mixture supplemented to diet may be helpful in preventing diabetic complications in adult rats.     

Antioxidant therapy and streptozotocin-induced diabetes in pregnant rats

The aim of our study was to analyse the effect of chronic hyperglycaemia on lipid peroxidation and scavenging enzyme activity in pregnant animals and their offspring supplemented and not supplemented with vitamin E – a natural antioxidant. Thirty pregnant female Wistar rats were used in our experiments. Diabetes was induced on day 7 of pregnancy using a single does of streptozotocin (40 mg/kg). Diabetic animals were divided into two equal groups: vitamin E supplemented and those fed with standard diet. Our controls consisted of 15 healthy rats. On day 1 after delivery homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn superoxide dismutase (SOD) and glutathione peroxidase (GPx) (Bioxytech, France). Statistical analysis was performed using Mann-Withney U test. The neonates of diabetic rats were smaller than those from healthy rats and serum glucose concentration was markedly higher in diabetic animals, both in mothers and neonates. MDA levels increased significantly, whereas GSH content and SOD as well as GPx activities were markedly diminished in diabetic pregnant rats and their offspring in comparison with the control group. In animals supplemented with tocopherol, MDA concentrations declined significantly, GSH contents and SOD activities were markedly elevated in almost all types of tissues studied, whereas glutathione peroxidase remained suppressed. Our results suggest that diabetic pregnant rats and their neonates are exposed to oxidative stress (OS), but vitamin E supplementation could in part reduce the imbalance between uncontrolled reactive oxygen species generation and scavenging enzyme activity, and may potentially serve as a useful prophylactic factor against OS development: Received: 4 January 1999 / Accepted in revised form: 19 May 1999     

Lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes

The aim of this study was to evaluate lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes, and then to establish whether moderate doses of nonenzymatic antioxidant vitamin E play a role in the antioxidant defence system in diabetic pregnant rats and their offspring. The study group consisted of 30 normal female Wistar rats, which were given a single dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the diabetic animals were divided into two matched groups: the first supplemented with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking vitamine E. Controls consisted of 15 pregnant rats. On the first day after delivery, the rats were decapitated and homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats were smaller than the healthy ones and serum glucose concentration was markedly higher in the diabetic animals. MDA levels were significantly increased, whereas GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their offspring in comparison to the control grouop. In the animals supplemented with α-tocopherol, MDA concentrations were significantly lower, GSH content and SOD activities were markedly elevated most tissues studied, whereas GPx remained unchanged. We conclude that, by monitoring the activity of selected scavenging enzymes, information on ongoing biological oxidative stress and thereby on the fetus/neonate status may be obtained. Our results suggest that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects. Received: 20 January 2000 / Accepted in revised form: 23 February 2001     

N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring

OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS: Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.     

Moderate exercise with a dietary vitamin C and e combination protects against streptozotocin-induced oxidative damage to the kidney and lens in pregnant rats.

Moderate exercise and vitamin C and E (VCE) supplementation can be beneficial to diabetes due to reducing free radical production in lens and kidney of diabetic pregnant rats. We investigated the effect of VCE supplementation and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the kidneys and lens of STZ-induced diabetic pregnant rats. Fifty female Wistar rats were used and were randomly divided into five groups. First and second were used as the control and pregnant control group. Third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Plasma, lens, and kidney samples were taken from all animals on day 20. Exercise and administration of VCE to pregnant diabetic rats resulted in significant decrease in the albumin and total protein values and the elevated MDA, plasma creatinine, and urea levels as an indicator of oxidative stress and renal functional parameters. Exercise and VCE supplementation also increased glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in the kidney, GSH-Px and GSH in the lens, the albumin and total protein values in plasma. In the diabetic pregnant animals, the decreased vitamins A and E concentration and GSH levels in kidney, creatinine, and urea values in plasma did not improve through exercise only although their concentrations were increased by VCE supplementation. Kidney weight did not also affect either by exercise or VCE supplementation. In conclusion, these results suggest that exercise plus VCE affects antioxidant metabolism and reduces lipid peroxidation, thereby improving the damage caused by oxidative stress involved in the pathogenesis of lens and kidney in diabetic pregnant rats. Moderate exercise with dietary VCE may play a role in preventing nephropathy and cataract formation in diabetic pregnant rat.     

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring

Summary Severe diabetes in pregnant rats produces persistent metabolic consequences in adult offspring. This study investigated whether diabetes in pregnant rats could also lead to cardiovascular abnormalities in the adult offspring. Blood pressure, heart rate and in vitro vascular reactivity of small arteries were evaluated in female adult offspring of control rats and of rats rendered diabetic with streptozotocin. Rise in blood pressures were similar in both groups of offspring but heart rate was lower in the diabetic offspring (p < 0.05). The rise in blood pressure associated with infusion of a nitric oxide synthase inhibitor was similar in both groups, but the associated decrease in heart rate was more pronounced in diabetic offspring (p < 0.01). Small mesenteric arteries from this group showed enhanced sensitivity to noradrenaline (p < 0.05) and abnormal endothelium-dependent relaxation to acetylcholine (p < 0.01) and bradykinin (p < 0.05). Reduction in acetylcholine induced relaxation, reflected reduced synthesis of nitric oxide or a cyclooxygenase product and was not attributable to an endothelium-derived hyperpolarizing factor. Sensitivity to exogenous nitric oxide was normal. A subgroup of pups born to diabetic dams were suckled by control maternal dams and a subgroup of those born to controls by diabetic dams. Suckling was an important determinant of impaired growth; offspring of diabetic rats suckled by their own mother and those of control rats by diabetic dams showed impaired growth rates whereas growth of offspring of diabetic rats suckled by control dams paralleled those of control rats suckled by their own mother. [Diabetologia (1999) 42: 81–89] Received: 29 May 1998 and in final form: 28 July 1998     

Amelioration of altered antioxidant enzymes activity and glomerulosclerosis by coenzyme Q10 in alloxan-induced diabetic rats

Coenzyme Q10 is a natural antioxidant and scavenging free radicals. In the present study, we examined antioxidative activities of coenzyme Q10 and possible protective effect of coenzyme Q10 on in vivo and in vitro lipid peroxidation, antioxidant enzymes activity and glomerulosclerosis in alloxan-induced type 1 diabetic rats. Thirty Sprague–Dawley male rats were divided into three groups randomly: group 1 as control, group 2 as diabetic untreatment, and group 3 as treatments with coenzyme Q10 by 15 mg/kg i.p. daily, respectively. Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, animals were anaesthetized, liver and kidney were then removed immediately and used fresh or kept frozen until their lipid peroxidation analysis. Blood samples were also collected before killing to measure the lipid peroxidation and antioxidant enzymes activity. Kidney paraffin sections were prepared and stained by periodic acid-Schiff method. Glomerular volume and leukocyte infiltration were estimated by stereological rules and glomerular sclerosis was studied semi-quantitatively. Coenzyme Q10 significantly inhibited leukocyte infiltration, glomerulosclerosis and the levels of malondialdehyde (MDA) serum and kidney content in treated group compared with the diabetic untreated group. Coenzyme Q10 significantly inhibited LDL oxidation in vitro. Coenzyme Q10 significantly increased the serum levels of glutathione (GSH) and serum activity of catalase (CAT) and superoxide dismutase (SOD) in treated group compared with the diabetic untreated group. Coenzyme Q10 alleviates leukocyte infiltration and glomerulosclerosis and exerts beneficial effects on the lipid peroxidation and antioxidant enzymes activity in alloxan-induced type 1 diabetic rats.     

The Effects of Combined Treatment of Antioxidants on the Liver Injury in STZ Diabetic Rats

The aim of this study was to examine whether an antioxidant combination of vitamin C, vitamin E, and sodium selenate (Se) has an effect on the liver of diabetic rats. Vitamin C, vitamin E, and Se were administered for 30 days to streptozotocin (STZ)-induced diabetic and control groups. In the STZ diabetic group, blood glucose levels, liver lipid peroxidation (LPO), and nonenzymatic glycosylation (NEG) levels increased, but blood and liver glutathione levels decreased. On the other hand, combined antioxidant treatment reversed these effects. In the diabetic group, some degenerative changes were observed by light and electron microscopic examinations, but the degenerative changes decreased in the diabetic group given antioxidant combination. Proliferating cell nuclear antigen (PCNA) immunohistochemistry showed that the number of proliferative hepatocytes increased significantly with antioxidant treatment. It was concluded that combined treatment with vitamin C, vitamin E, and Se has a curative effect against the hepatotoxicity produced by STZ-induced diabetes.     

An imbalance in the methionine content of the maternal diet reduces postnatal growth in the rat

The pregnant rat fed a low-protein diet has become widely used as a model system in the study of the prenatal programming of adult metabolism and disease. When pregnant rats of the hooded Lister strain were fed semisynthetic diets containing 18% or 9% casein supplemented with 0.5% dl-methionine, there was significant postnatal mortality in the group fed the low-protein diet. In a second experiment, dams were fed diets containing 9% casein supplemented with varying concentrations of dl-methionine up to 0.4% (w/w) and compared with a group fed a diet containing 18% casein supplemented with 0.5% dl-methionine. At birth, the pups from dams fed the low-protein diets supplemented with 0.2% dl-methionine or greater were significantly smaller than those of the dams fed the diet containing 18% protein. By 25 weeks of age, the body weight of the offspring of dams fed the low-protein diet supplemented with 0.2% or 0.3% dl-methionine were approximately 10% lower than those in the control group of offspring from dams fed 18% protein supplemented with 0.5% dl-methionine. There were corresponding changes in the weights of the major organs. These data suggest that increasing the dl-methionine supplement in the low-protein diet retards the growth of the fetus and affects the mature adult body weight. In contrast to the findings of other studies that used different formulas of the low-protein diet, the glucose tolerance in the offspring was unaffected by the protein content of the maternal diet at all levels of dl-methionine supplementation. These results suggest that the changes in metabolism of the offspring result from interactions between protein, lipids, and carbohydrates in the maternal diet, rather than a consequence of postnatal growth retardation per se and highlight the importance of considering all components of the maternal diet in the programming mechanism.     

Different diabetogenic response to moderate doses of streptozotocin in pregnant rats, and its long-term consequences in the offspring

Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases. Experimental models are still needed to investigate the mechanism responsible for these alterations. Thus, by the administration of different doses of streptozotocin (STZ) (0, 25, 30, or 35 mg/kg body weight, intravenous) at the onset of pregnancy in rats, the present study sought an appropriate animal model for this pathology. At day 6 of pregnancy, plasma glucose was progressively higher with an increasing STZ dose, and in rats receiving the 35-mg dose, 2 subgroups were detected: some animals had plasma glucose levels above controls but below 200 mg/dL (mildly diabetic, MD), whereas others had levels above 400 mg/dL (severely diabetic, SD). At day 20 of pregnancy, the MD rats had normal glycemia, but after an oral glucose load (2 g/kg body weight), plasma glucose increased more and insulin increased less than in controls. The SD rats maintained their hyperglycemia and had a greatly impaired oral glucose tolerance. At day 20, fetuses of SD dams were fewer, weighed less, and had enhanced plasma glucose and triglycerides and decreased insulin, whereas those from MD dams did not differ from controls. At birth, newborns from MD dams had higher body weight, plasma insulin, and liver triglycerides as well as total body lipid concentrations than controls, and on day 21, remained macrosomic and showed higher plasma glucose and liver triglyceride concentrations. At 70 days of age, offspring of MD dams had impaired oral glucose tolerance but normal plasma insulin change in the case of females, whereas plasma insulin increased less in males. These alterations were manifest more in those offspring from dams that had >50% macrosomic newborns than in those from dams that had <50% macrosomic newborns. In conclusion, whereas our MD rats mimic the changes taking place in gestational diabetic women and show the long-term risk of macrosomia, the SD rats are more similar to uncontrolled diabetics. Thus these two rat models, obtained with moderate amounts of STZ, could be used to study the pathophysiological consequences of these different diabetic conditions.     

Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus

There is a clearly documented link between diabetic complications and lipid peroxidation. Hyperglycemia causes a reduction in levels of protective endogenous antioxidants and increases generation of free radicals. The present study was carried out to compare the protective effects of melatonin and vitamin E against streptozocin (STZ)-induced diabetes in rats. Melatonin was administered s.c. (100 microg/kg) whereas vitamin E was given i.p. (100 mg/kg) after induction of diabetes with STZ (60 mg/kg). Plasma total cholesterol, triglyceride and low density lipoprotein (LDL) levels were increased in STZ group while both melatonin and vitamin E injection caused a significant decrease in the levels of all these parameters. The lipid lowering effect of melatonin was greater than that of vitamin E. Melatonin caused a significant decrease in brain, liver and kidney tissue malondialdehyde (MDA) levels which were increased because of STZ-induced diabetes. Vitamin E also reduced elevated MDA concentrations in diabetic rat tissues, but the effect of melatonin was more potent than that of vitamin E. Furthermore, treatment of diabetic rats with melatonin increased brain and kidney glutathione peroxidase (GSH-Px) activity to the levels below that of control rats. Vitamin E was found to be less effective on GSH-Px activity levels in brain and kidney than melatonin whereas it was more potent than melatonin in liver. In summary, melatonin prevents many diabetic complications by reducing oxidative stress and protects organisms from oxidative damage and dyslipidemia. Considering the much lower molar concentration of melatonin compared with vitamin E, melatonin seems to be a more potent antioxidant, especially in the brain and kidney.     

The effect of maternal diabetes on the synthesis and secretion of phosphatidylcholine in fetal and maternal rat lungs in vitro

Summary Incorporation of (methyl-¹⁴C)choline into phosphatidylcholine and the release of prelabelled phosphatidylcholine was investigated in vitro using lung slices from pregnant rats and their offspring near term. Tissue from normal, diabetic and insulin-treated diabetic pregnant rats and their offspring was utilized to assess the effects of maternal diabetes on fetal lung maturation. The results show that the synthesis of phosphatidylcholine in fetal/newborn lungs through the cytidine 5-diphosphocholine pathway was not affected by maternal diabetes. However, secretion of phosphatidylcholine from the lungs of fetuses of diabetic mothers was very much suppressed one day after parturition. Insulin treatment of the diabetic pregnant rats restored secretion of phosphatidylcholine from the fetal/newborn lungs to control values. These re sults suggest that an impaired secretion of phosphatidylcholine from the lungs of fetuses of diabetic mothers may be partly responsible for the higher incidence of respiratory distress syndrome among children of diabetic mothers. The results also revealed some correlation between the secretion of phosphatidylcholine from maternal lungs, maternal serum phospholipids and synthesis of phosphatidylcholine by fetal lungs during late gestation, suggesting a possible relationship between maternal phospholipid metabolism and fetal lung maturation.     

Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats

Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats each [control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (P<0.001 and P<0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ-induced experimental diabetes and indicate the beneficial free radical-scavenging and antioxidant properties of melatonin.     

Modulation of antioxidant status in streptozotocin-induced diabetic male wistar rats following intake of red palm oil and/or rooibos

Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.     

Characterization of oxidative stress in various tissues of diabetic and galactose-fed rats

Rats fed a galactose-rich diet have been used for several years as a model for diabetes to study, particularly in the eye, the effects of excess blood hexoses. This study sought to determine the utility of galactosemia as a model for oxidative stress in extraocular tissues by examining biomarkers of oxidative stress in galactose-fed rats and experimentally-induced diabetic rats. Sprague-Dawley rats were divided into four groups: experimental control; streptozotocin-induced diabetic; insulin-treated diabetic; and galactose-fed. The rats were maintained on these regimens for 30 days, at which point the activities of catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase, as well as levels of lipid peroxidation and reduced and oxidized glutathione were determined in heart, liver, and kidney. This study indicates that while there are some similarities between galactosemic and diabetic rats in these measured indices of oxidative stress (hepatic catalase activity levels and hepatic and renal levels of oxidized glutathione in both diabetic and galactosemic rats were significantly decreased when compared to normal), overall the galactosemic rat model is not closely parallel to the diabetic rat model in extra-ocular tissues. In addition, several effects of diabetes (increased hepatic glutathione peroxidase activity, increased superoxide dismutase activity in kidney and heart, decreased renal and increased cardiac catalase activity) were not mimicked in galactosemic rats, and glutathione concentration in both liver and heart was affected in opposite ways in diabetic rats and galactose-fed rats. Insulin treatment reversed/prevented the activity changes in renal and cardiac superoxide dismutase, renal and cardiac catalase, and hepatic glutathione peroxidase as well as the hepatic changes in lipid peroxidation and reduced and oxidized glutathione, and the increase in cardiac glutathione. Thus, prudence should be exercised in the use of experimentally galactosemic rats as a model for diabetes until the correspondence of the models has been more fully characterized.     

Maternal diabetes compromises the organization of hypothalamic feeding circuits and impairs leptin sensitivity in offspring

Maternal diabetes is a common complication of pregnancy, and the offspring of diabetic mothers have a higher risk of developing obesity and type 2 diabetes later in life. Despite these observations, the precise biological processes mediating this metabolic programming are not well understood. Here, we explored the consequences of maternal diabetes on the organization of hypothalamic neural circuits involved in the regulation of energy balance. To accomplish this aim, we used a mouse model of maternal insulin deficiency induced by streptozotocin injections. Maternal diabetes was found to be associated with changes in offspring growth as revealed by a significantly higher pre- and postweaning body weight in the offspring of insulin-deficient dams relative to those of control mice. Mice born to diabetic dams also showed increased fasting glucose levels, increased insulin levels, and increased food intake during their adult lives. These impairments in metabolic regulation were associated with leptin resistance during adulthood. Importantly, the ability of leptin to activate intracellular signaling in arcuate neurons was also significantly reduced in neonates born to diabetic dams. Furthermore, neural projections from the arcuate nucleus to the paraventricular nucleus were markedly reduced in the offspring of insulin-deficient dams. Together, these data show that insulin deficiency during gestation has long-term consequences for metabolic regulation. They also indicate that animals born to diabetic dams display abnormally organized hypothalamic feeding pathways that could result from the attenuated responsiveness of hypothalamic neurons to the neurotrophic actions of leptin during neonatal development.     

Blood levels of insulin-like growth factors I and II in neonates of non-insulin-dependent diabetic rats

Circulating levels of insulin like growth factor I (IGF-I) and insulin like growth factor II (IGF-II) were evaluated in plasma samples during the first 72 h of life in neonates of diabetic and control mother rats. Diabetes had been induced in the diabetic dams by streptozotocin at 2 days of age. The rats developed non-insulin dependent diabetes (at 6 weeks of age) and became pregnant at 11 weeks of age. Maternal blood glucose levels were higher in the diabetic mothers (P<0.05) during the last two-thirds of gestation. Complications occurred at the end of 7.1% of the diabetic pregnancies but none of the controls. Analysis of neonates plasma glucose, IGF-I, and IGF-II concentrations in the first 12, 24, 48, and 72 h after birth revealed higher glucose levels in neonates of diabetic mothers at 72 h compared with controls (118±7 vs 85±5 mg/dl,P<0.05) but there was no difference in IGF-I or IGF-II levels between the groups at any time point. Thus, acquired impaired glucose homeostasis may be seen in neonates of mildly diabetic mothers at early stages of their life but their circulating insulin-like growth factors levels are normal. These data do not support the proposition that fetal IGF-I and —II affect the outcome of pregnancies complicated by mild diabetes in the rodent.     

Antioxidant effect of vanadate on experimental diabetic rats

Summary The activities of enzymes involved in cellular defence mechanisms such as superoxide dismutase, catalase, glutathione peroxidase and glutathione level have been found to be altered in experimental diabetes. Rats were made diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight) in citrate buffer. After the onset of diabetes, the diabetic rats were treated with sodium orthovanadate (0.3 mg/ml) for 15 days. Decreased activities of glutathione peroxidase, catalase, superoxide dismutase and glutathione content found in diabetic rats were corrected to near normal. The altered levels of plasma lipid peroxide, glycoproteins and erythrocyte membrane phospholipids in diabetic rats were restored to control levels by vanadate treatment. These observations clearly indicate the antioxidant potential of vanadate on experimental diabetes.     

The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose-6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver

Abstract Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses the conjugation of glutathione with a variety of organic peroxides to form more water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential to control intracellular reductive potential by increasing glutathione intracellular levels, which in turn decrease the amount of reactive oxygen species. Glyburide decreases glucose production and enhances insulin action in liver. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the liver tissue of diabetic rat. We investigated the activities of GST and G6PDH in the liver of both control and streptozotocin-induced diabetic rats. Forty male albino rats were included in this study. Liver GST and G6PDH activities decreased significantly in five-week diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration suggest that glyburide may directly alter hepatic enzyme activities.     

Hypoglycemic effect of Costus pictus D. Don on alloxan induced type 2 diabetes mellitus in albino rats

ObjectiveTo demonstrate the effect of aqueous extract of Costus pictus (C. pictus) leaves on blood glucose, lipid profile and liver antioxidant enzymes and lipid peroxidation in alloxan induced diabetic rats.MethodsAqueous extract of C. pictus (AECP) leaves was administered orally for 30 days and its effect on blood glucose, lipid profile, hepatic marker enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum urea, creatinine, protein and albumin content and liver antioxidant enzymes such as catalase, peroxidase, superoxide dismutase and lipid peroxidation in alloxan induced diabetic rats were examined.ResultsOral administration of aqueous extract of C. pictus leaves to diabetic rats for 30 days significantly reduced the levels of blood glucose, lipid profile, lipid peroxidation, liver marker enzymes, urea, creatinine and increased the levels of antioxidant enzymes.ConclusionsThe aqueous extract of C. pictus leaves controls the blood glucose level, improves lipid metabolism and prevents diabetic complications associated with lipid peroxidation and also maintains the antioxidant enzymes in experimental diabetic rats. Therefore, it can be recommeded for the prevention of diabetes mellitus.