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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymes of glucose and lipid metabolism are markedly altered in experimental diabetes. In the present study, we investigated the effect of tetrahydrocurcumin (THC), one of the active metabolites in curcumin, on the key hepatic metabolic enzymes involved in carbohydrate metabolism in streptozotocin-induced diabetic rats. Different doses of THC (20, 40, and 80 mg\kg body weight) were orally administered to diabetic rats for 45 days. The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, fructose-1,6-bisphosphatase, and sorbitol dehydrogenase in liver, and glycogen content in liver and muscle were assayed. In untreated diabetic control rats, the activities of the gluconeogenic enzymes were significantly increased, whereas hexokinase and G6PD activity and glycogen levels were significantly decreased. Both THC and curcumin were able to restore the altered enzyme activities to near normal levels. Tetrahydrocurcumin was more effective than curcumin. Our results indicate that the administration of THC to diabetic animals normalizes blood glucose and causes a marked improvement of altered carbohydrate metabolic enzymes.
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PMID:Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats. 1643 92

Several studies have shown impairment of neutrophil function, a disorder that contributes to the high incidence of infections in diabetes. Since glucose and glutamine play a key role in neutrophil function, we investigated their metabolism in neutrophils obtained from the peritoneal cavity of streptozotocin-induced diabetic rats. The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), citrate synthase, phosphate-dependent glutaminase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were assayed. Glucose, glutamine, lactate, glutamate and aspartate, and the decarboxylation of [U-14C], [1-14C] and [6-14C]glucose; [U-14C]palmitic acid; and [U-14C]glutamine were measured in 1-h incubated neutrophils. Phagocytosis capacity and hydrogen peroxide (H2O2) production were also determined. All measurements were carried out in neutrophils from control, diabetic and insulin-treated (2-4 IU/day) diabetic rats. Phagocytosis and phorbol myristate acetate (PMA)-stimulated H2O2 production were decreased in neutrophils from diabetic rats. The activities of G6PDH and glutaminase were decreased, whereas that of PFK was raised by the diabetic state. The activities of the remaining enzymes were not changed. Diabetes decreased the decarboxylation of [1-14C]glucose and [U-14C]glutamine; however, [6-14C]glucose and [U-14C]palmitic acid decarboxylation was increased. These observations indicate that changes in metabolism may play an important role in the impaired neutrophil function observed in diabetes. The treatment with insulin abolished the changes induced by the diabetic state even with no marked change in glycemia. Therefore, insulin may have a direct effect on neutrophil metabolism and function.
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PMID:Diabetes causes marked changes in function and metabolism of rat neutrophils. 1646 55

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.
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PMID:Intestinal disaccharidases and some renal enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides). 1649 37

Trigonella foenum graecum seed powder (TSP) and Sodium Orthovanadate (SOV) have been shown to demonstrate antidiabetic effects by stabilizing glucose homeostasis and carbohydrate metabolism in experimental type-1 diabetes. However their efficacy in controlling histopathological and biochemical abnormalities in ocular tissues associated with diabetic retinopathy is not known. The purpose of this study was to investigate the comparative efficacy of individual as well as combination therapy of TSP and SOV in 8 weeks diabetic rat lens and retina. Retinas and lenses were taken from control, alloxan-induced diabetic rats and diabetic rats treated separately with insulin, 5%TSP, SOV (0.6 mg/ml) and a combined dose of SOV (0.2 mg/ml) and 5%TSP for 60 days. Control and each experimental group had six rats. Alterations in the activities of enzymes HK (hexokinase), AR (aldose reductase), SDH (sorbitol dehydrogenase), G-6-PD (glucose-6-phosphate dehydrogenase), GPx (glutathione peroxidase), GR (glutathione reductase) and levels of metabolites like sorbitol, fructose, glucose, MDA (malondialdehyde) and GSH (reduced glutathione) were measured in the cytosolic fraction of lenses besides measuring blood glucose levels and glycosylated haemoglobin. Histopathological abnormalities were studied in the lens using photomicrography and retina using transmission electron microscopy. Blood glucose, glycosylated haemoglobin levels and polyol pathway enzymes AR and SDH increased significantly causing accumulation of sorbitol and fructose in the diabetic lens and treatment with SOV and TSP significantly (p < 0.05) decreased these to control levels. Similarly, SOV and TSP treatments modulated the activities of HK, G-6-PD, GPx and GR in the rat lens to control values. Ultrastructure of the diabetic retina revealed disintegration of the inner nuclear layer cells with reduction in rough endoplasmic reticulum and swelling of mitochondria in the bipolar cells; and these histopathological events were effectively restored to control state by SOV and TSP treatments. In this study SOV and TSP effectively controlled ocular histopathological and biochemical abnormalities associated with experimental type-1 diabetes, and a combination regimen of low dose of SOV with TSP demonstrated the most significant effect. In conclusion, the potential of SOV and TSP alone or in low dose combination may be considered as promising approaches for the prevention of diabetic retinopathy and other ocular disorders.
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PMID:Long-term effect of Trigonella foenum graecum and its combination with sodium orthovanadate in preventing histopathological and biochemical abnormalities in diabetic rat ocular tissues. 1671 75

Carbohydrate metabolism is impaired in diabetes. The resultant hyperglycemia could cause tremendous changes in the metabolic activities of the liver. We therefore designed this study to investigate the effects of caloric restriction, which has been shown to improve blood glucose homeostasis, on carbohydrate metabolism in the livers of non-diabetic and streptozotocin-induced diabetic rats. Forty male Wistar rats were divided into two groups of caloric restricted (CR) and ad libitum (AL) fed rats. The caloric restricted animals were subjected to 30% caloric restriction. Feeding experiments were conducted for 9 weeks before the induction of diabetes in 50% of the groups. Caloric restriction was found to significantly decrease glycogen (p<0.001), hepatic glucose (p<0.01), phosphofructokinase (p<0.05), glucokinase (p<0.05), aldose reductase (p<0.05), and sorbitol dehydrogenase (p<0.05) and significantly increase hexokinase (p<0.001), glucose-6-phosphate dehydrogenase (p<0.05), and glucose-6-phosphatase activities (p<0.05) in diabetic and non-diabetic rats. From our results, it is suggested that alteration of the metabolic pathways involved in glucose metabolism in the liver could be one of the various ways in which CR attenuates hyperglycemic effects in diabetes.
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PMID:Modulation of the flux patterns in carbohydrate metabolism in the livers of streptozoticin-induced diabetic rats by dietary caloric restriction. 1674 Mar 92

Low-dose acetylsalicylic acid (ASA) treatment is a standard therapeutic approach in diabetes mellitus for prevention of long-term vascular complications. The aim of the present work was to investigate the effect of long-term ASA administration in experimental diabetes on activities of some liver enzymes: glutathione peroxidase (GSHPx), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST). Blood glucose, glycated hemoglobin, as well as plasma ALT and AST activities increased in rats with streptozotocin-induced experimental diabetes. The long-term hyperglycemia resulted in decreased activities of GSHPx (by 26%), catalase (by 34%), GST (by 38%) and G6PDH (by 27%) in diabetic animals. We did not observe increased accumulation of membrane lipid peroxidation products or altered levels of reduced glutathione in livers. The linear correlation between blood glucose and glycated hemoglobin in diabetic animals was distorted upon ASA treatment, which was likely due to a chemical competition between nonenzymatic protein glycosylation and protein acetylation. The long-term ASA administration partially reversed the decrease in GSHPx activity, but did not influence the activities of catalase and GST in diabetic rats. Otherwise, some decrease in these parameters was noted in ASA-treated nondiabetic animals. Increased ASA-induced G6PDH activity was recorded in both diabetic and nondiabetic rats. While both glycation due to diabetic hyperglycemia and ASA-mediated acetylation had very similar effects on the activities of all studied enzymes but G6PDH, we conclude that non-enzymatic modification by either glucose or ASA may be a common mechanism of the observed convergence.
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PMID:Antioxidative enzyme and glutathione S-transferase activities in diabetic rats exposed to long-term ASA treatment. 1681 74

Free radicals and associated oxidative stress induced by alloxan are implicated in eliciting pathological changes in diabetes mellitus. Terminalia arjuna bark, an indigenous plant used in ayurvedic medicine in India, primarily as a cardiotonic is also used in treating diabetes, anemia, tumors and hypertension. The present study examined the effect of ethanolic extract (250 and 500 mg/kg body weight) of Terminalia arjuna stem bark in alloxan induced diabetic rats and its lipid peroxidation, enzymatic and nonenzymatic activity was investigated in the liver and kidney tissues. The extract produced significant (P<0.05) reduction in lipid peroxidation (LPO). The effect of oral T. arjuna at the dose of 500 mg/kg body weight was more than the 250 mg/kg body weight. The extract also causes a significant (P<0.05) increase in superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase glutathione reductase and glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin A, vitamin C, vitamin E, total sulfhydryl groups (TSH) and non protein sulfhydryl groups (NPSH) in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of T. arjuna bark. The result indicates that the extract exhibit the antioxidant activity through correction of oxidative stress and validates the traditional use of this plant in diabetic animals.
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PMID:Effect of Terminalia arjuna stem bark on antioxidant status in liver and kidney of alloxan diabetic rats. 1705 32

Cardiovascular complications of diabetes mellitus involve oxidative stress and profound changes in reduced glutathione (GSH), an essential tripeptide that controls many redox-sensitive cell functions. This study examined regulation of GSH by insulin to identify mechanisms controlling cardiac redox state and to define the functional impact of GSH depletion. GSH was measured by fluorescence microscopy in ventricular myocytes isolated from Sprague-Dawley rats made diabetic by streptozotocin, and video and confocal microscopy were used to measure mechanical properties and Ca(2+) transients, respectively. Spectrophotometric assays of tissue extracts were also done to measure the activities of enzymes that control GSH levels. Four weeks after injection of streptozotocin, mean GSH concentration ([GSH]) in isolated diabetic rat myocytes was approximately 36% less than in control, correlating with decreased activities of two major enzymes regulating GSH levels: glutathione reductase and gamma-glutamylcysteine synthetase. Treatment of diabetic rat myocytes with insulin normalized [GSH] after a delay of 3-4 h. A more rapid but transient upregulation of [GSH] occurred in myocytes treated with dichloroacetate, an activator of pyruvate dehydrogenase. Inhibitor experiments indicated that insulin normalized [GSH] via the pentose pathway and gamma-glutamylcysteine synthetase, although the basal activity of glucose-6-phosphate dehydrogenase was not different between diabetic and control hearts. Diabetic rat myocytes were characterized by significant mechanical dysfunction that correlated with diminished and prolonged Ca(2+) transients. This phenotype was reversed by in vitro treatment with insulin and also by exogenous GSH or N-acetylcysteine, a precursor of GSH. Our data suggest that insulin regulates GSH through pathways involving de novo GSH synthesis and reduction of its oxidized form. It is proposed that a key function of glucose metabolism in heart is to supply reducing equivalents required to maintain adequate GSH levels for the redox control of Ca(2+) handling proteins and contraction.
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PMID:Insulin regulation of glutathione and contractile phenotype in diabetic rat ventricular myocytes. 1705 75

In adipocytes, oxidative stress and chronic inflammation are closely associated with metabolic disorders, including insulin resistance, obesity, cardiovascular disease, and type 2 diabetes. However, the molecular mechanisms underlying these metabolic disorders have not been thoroughly elucidated. In this report, we demonstrate that overexpression of glucose-6-phosphate dehydrogenase (G6PD) in adipocytes stimulates oxidative stress and inflammatory responses, thus affecting the neighboring macrophages. Adipogenic G6PD overexpression promotes the expression of pro-oxidative enzymes, including inducible nitric oxide synthase and NADPH oxidase, and the activation of nuclear factor-kappaB (NF-kappaB) signaling, which eventually leads to the dysregulation of adipocytokines and inflammatory signals. Furthermore, secretory factors from G6PD-overexpressing adipocytes stimulate macrophages to express more proinflammatory cytokines and to be recruited to the adipocytes; this would cause chronic inflammatory conditions in the adipose tissue of obesity. These effects of G6PD overexpression in adipocytes were abolished by pretreatment with NF-kappaB inhibitors or antioxidant drugs. Thus, we propose that a high level of G6PD in adipocytes may mediate the onset of metabolic disorders in obesity by increasing the oxidative stress and inflammatory signals.
Diabetes 2006 Nov
PMID:Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals. 1706 29

1. Diabetes mellitus is a serious metabolic disorder with micro- and macrovascular complications that results in significant morbidity and mortality. 2. The aim of the present study was to evaluate the hypoglycaemic efficacy of commonly used traditional Indian plants, such as Murraya koenigii, Mentha piperitae, Ocimum sanctum and Aegle marmelos, in streptozotocin (STZ)-induced experimental rats. 3. Oral administration of the ethanolic extract of these plants resulted in a significant decrease in the levels of blood glucose, glycosylated haemoglobin and urea, with a concomitant increase in glycogen, haemoglobin and protein, in diabetic rats. Treatment with these plant extracts also resulted in an increase in insulin and C-peptide levels and glucose tolerance. 4. The decreased activities of carbohydrate-metabolising enzymes, such as hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthase, in diabetic rats were significantly elevated towards near normal in rats treated with extracts of M. koenigii, O. sanctum and A. marmelos; the increased activities of lactate dehydrogenase, fructose-1,6-bisphosphatase, glucose-6-phosphatase and glycogen phosphorylase in STZ diabetic rats were significantly reduced following treatment with the plant extracts. 5. Elevated specific binding of [(125)I]-labelled insulin to the receptor found in diabetic rats was markedly decreased in extract-treated groups. However, treatment of diabetic rats with M. piperitae did not result in any significant modification in all parameters. 6. Phytochemical screening conducted by us revealed the presence of biologically active ingredients in the ethanolic extracts of M. koenigii, O. sanctum and A. marmelos, which may readily account for the observed hypoglycaemic activity.
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PMID:Biochemical evaluation of antidiabetogenic properties of some commonly used Indian plants on streptozotocin-induced diabetes in experimental rats. 1718 94


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