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Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

Context: The health benefits and medicinal properties of herbal food products are known since antiquity. Fenugreek [Trigonella foenum-graecum Linn. (Fabaceae)], a seed spice used to enhance flavor, color and texture of food, is employed for medicinal purposes in many traditional systems. A number of epidemiological studies and laboratory research have unraveled the biological actions of fenugreek., Objective: Research on fenugreek in recent years has identified a number of health benefits and physiological attributes in both experimental animals as well as clinical trials in humans. In this study we have reviewed the available scientific literature on fenugreek., Methods: This review article summarizes and reviews published experimental studies and scientific literature from the databases including PubMed, Google and local library searches., Results: The information available in the literature on the health benefits and pharmaceutical effects of Trigonella accounts for its known medicinal properties and adds new therapeutic effects in newer indications. Besides its known medicinal properties such as carminative, gastric stimulant, antidiabetic and galactogogue (lactation-inducer) effects, newer research has identified hypocholesterolemic, antilipidemia, antioxidant, hepatoprotective, anti-inflammatory, antibacterial, antifungal, antiulcer, antilithigenic, anticarcinogenic and other miscellaneous medicinal effects of fenugreek. Although most of these studies have used whole seed powder or different forms of extracts, some have identified active constituents from seeds and attributed them medicinal values for different indications., Conclusion: The resarch on Trigonella exhibits its health benefits and potential medicinal properties in various indications and has little or no side effects, suggesting its pharmaceutical, therapeutic and nutritional potential.

Oxidative stress in diabetic tissues is accompanied by high-level of free radicals with simultaneously declined antioxidant enzymes status leading to cell membrane damage. The present study was carried out to observe the effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, antioxidant enzymes, lipid peroxidation, pyruvate kinase, lactate dehydrogenase and protein kinase C in heart, muscle and brain of the alloxan-induced diabetic rats to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight), and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for 21 days. Blood glucose levels increased markedly in diabetic rats, animals treated with a combined dose of SOV and TSP had glucose levels almost comparable with controls, similar results were obtained in the activities of pyruvate kinase, lactate dehydrogenase, antioxidant enzymes and protein kinase C in diabetic animals. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP to effectively reverse diabetic alterations in experimental diabetes., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Trigonella foenum-graecum, an annual herb belonging to the family Leguminosae, commonly known as fenugreek, has been reported to have hypoglycemic, hypocholesterolemic, hyperinsulinemic and antidiabetic properties. In the present study, the effect of oral feeding of Trigonella foenum-graecum seed powder (TSP) has been studied on blood glucose, monoamine oxidase (MAO), membrane fluidity, neurolipofuscin content, DNA degradation and glucose transporter-4 (GLUT4) accumulation in the alloxan-induced diabetic rat brain., Methods: Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and diabetic rats were treated with 2 IU insulin, per day and 5% TSP in the diet for 21 days., Results: Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Increased MAO activity with correlated increase in genomic DNA degradation in the diabetic brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress, causing loss of membrane fluidity, increased neurolipofuscin and decreased of GLUT4 expression with diabetes in the brain. The present study showed that TSP treatment reversal the changes to near normal levels in diabetic rat brain., Conclusions: The present findings indicate that the TSP exerts its anti-diabetic and neuroprotective effects, probably mediated through a decrease in hyperglycemia and oxidative stress thereby ameliorating the control and management of diabetic complications.

Trigonella foenum-graecum seed powder (TSP) has been reported to have hypoglycemic and hyperinsulinemic action. The objective of the study was to examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced alterations in blood glucose, insulin levels and activities of membrane linked enzymes (Na+K+ATPase, Ca2+ATPase), antioxidant enzymes (superoxide dismutase, glutathione S-transferase), calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female Wistar rats weighing between 180 and 220 g were made diabetic by a single injection of alloxan monohydrate (15 mg/100 g body weight), diabetic rats were given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A significant increase in lipid peroxidation was observed in diabetic brain. The increased lipid peroxidation following chronic hyperglycemia was accompanied with a significant increase in the neurolipofuscin deposition and Ca2+ levels with decreased activities of membrane linked ATPases and antioxidant enzymes in diabetic brain. A decrease in synaptosomal membrane fluidity may influence the activity of membrane linked enzymes in diabetes. The present study showed that TSP treatment can reverse the hyperglycemia induced changes to normal levels in diabetic rat brain. TSP administration amended effect of hyperglycemia on alterations in lipid peroxidation, restoring membrane fluidity, activities of membrane bound and antioxidant enzymes, thereby ameliorating the diabetic complications.

Biological aging is a fundamental process observed in almost all living beings. During aging the brain experiences structural, molecular, and functional alterations. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to investigate the anti-aging and protective potential of 17β estradiol (E2) treatment on activities of membrane linked ATPases (Na⁺K⁺ ATPase, Ca²⁺ATPase), antioxidant enzymes (superoxide dismutases, glutathione-S-transferases), intrasynaptosomal calcium levels, membrane fluidity and neurolipofuscin in the brain of aging female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of E2 (0.1 μg/g body weight for one month).The results obtained in the present work revealed that normal aging was associated with significant decrease in the activities of membrane linked ATPases, antioxidant enzymes and an increase in neurolipofuscin, intrasynaptosomal calcium levels in brain of aging female rats. The present study showed that E2 treatment reversed the changes to near normal levels. E2 treatment appears to be beneficial in preventing some of the age related changes in the brain, an important anti-aging effect of the hormone., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmacokinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and antihyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.

Free radical production and oxidative stress are known to increase in liver during aging, and may contribute to the oxidative damage. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of membrane linked ATPases (Na(+)K(+) ATPase, Ca(2+) ATPase), antioxidant enzymes (superoxide dismutase, glutathione-S-transferase), lipid peroxidation levels, lipofuscin content and membrane fluidity occurring in livers of female rats of 3, 12 and 24 months age groups, and to see whether these changes are restored to 3 months control levels rats after exogenous administration of 17-β-estradiol (E2). The aged rats (12 and 24 months) were given subcutaneous injection of E2 (0.1 μg/g body weight) daily for one month. The results obtained in the present work revealed that normal aging was associated with significant decrease in the activities of membrane linked ATPases, antioxidant enzymes, membrane fluidity and an increase in lipid peroxidation and lipofuscin content in livers of aging female rats. The present study showed that E2 treatment reversed the changes to normal levels. E2 treatment may be beneficial in preventing some of the age related changes in the liver by increasing antioxidant defenses.

Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.

Influence of exogenously administered dehydroepiandrosterone (DHEA) on the activity of Na+ K+ ATPase was investigated in synaptosomal fraction from cerebral cortex, cerebellum, hippocampus and medulla regions of brain of 12 and 22 months old rats. DHEA was administered daily at the dose of 30 mg/kg/body wt, intraperitonially (ip) in both the age groups of rats for 1 month. Results showed that Na+ K+ ATPase activity, increased in DHEA treated rats in both the age groups. In terms of per cent increase, 22 months old animals showed significant increase in Na+ K+ ATPase activity in the synaptosomal fraction of all the four brain regions than in 12 months old DHEA-treated rats. This showed that exogenous DHEA modulated the activity of Na+ K+ ATPase and also protected the age-related loss of membrane integrity and functions. It was concluded that exogenous DHEA might be beneficial in terms of neuroprotection against age-related loss of Na+ K+ ATPase mediated brain functions like learning and memory.

Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders.

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.

Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.

Oral administration of vanadate to diabetic animals have been shown to stabilize the glucose homeostasis and restore altered metabolic pathways. However, vanadate exerts these effects at relatively high doses with several toxic effects. Low doses of vanadate are relatively safe but unable to elicit any antidiabetic effects. The present study explored the prospect of using low doses of vanadate with Trigonella foenum graecum, seed powder (TSP), another antidiabetic agent, and to evaluate their antidiabetic effect in diabetic rats. Alloxan diabetic rats were treated with insulin, vanadate, TSP and low doses of vanadate with TSP for three weeks. The effect of these antidiabetic compounds was examined on general physiological parameters, Na(+)/K(+) ATPase activity, membrane lipid peroxidation and membrane fluidity in liver, kidney and heart tissues. Expression of glucose transporter (GLUT4) protein was also examined by immunoblotting method in experimental rat heart after three weeks of diabetes induction. Diabetic rats showed high blood glucose levels. Activity of Na(+)/K(+) ATPase decreased in diabetic liver and heart. However, kidney showed a significant increase in Na(+)/K(+) ATPase activity. Diabetic rats exhibited an increased level of lipid peroxidation and decreased membrane fluidity. GLUT4 distribution was also significantly lowered in heart of alloxan diabetic rats. Treatment of diabetic rats with insulin, TSP, vanadate and a combined therapy of lower dose of vanadate with TSP revived normoglycemia and restored the altered level of Na(+)/K(+) ATPase, lipid peroxidation and membrane fluidity and also induced the redistribution of GLUT4 transporter. TSP treatment alone is partially effective in restoring the above diabetes-induced alterations. Combined therapy of vanadate and TSP was the most effective in normalization of altered membrane linked functions and GLUT4 distribution without any harmful side effect.

Recently it has been found that Candida albicans harbours enzymes involved in the glyoxylate cycle (GC), which have a role in its virulence, especially the two key enzymes, isocitrate lyase (ICL) and malate synthase (MS). There are however, few studies on the GC enzyme activities isolated in the clinical isolates. Samples were collected from three groups of patients namely, HIV/AIDS, diabetic and burn patients suffering from candidiasis at different body locations. Isolation, identification and the antifungal susceptibility test of all the isolates of C. albicans were followed by the standard techniques. Measurements of all the GC enzyme activities were also carried out by the standard methods. Levels of the principal GC enzymes showed significant changes when calculated and compared taking control strains of C. albicans. The activity of the two key enzymes of the GC, ICL and MS were significantly higher in the isolates from diabetic patients. No significant relationship between the drug susceptibility and the level of enzymes of the GC was observed. As GC activity is absent in mammalian cells, a specific inhibitor for the GC could be developed and these enzymes therefore can be used as a new antifungal target.

The brain tissue has a large oxidative capacity, but its ability to combat oxidative stress is limited. In aging brain tissue the oxidative stress increases due to decreased activity of antioxidant enzymes and increased oxidative stress leading to neurodegeneration associated with excitotoxicity. The aim of the present study was to determine the effect of neuropeptides, neurokinin B (NKB) and amyloid beta protein fragment Abeta (25-35) and neurotransmitters N-methyl D-aspartate (NMDA) and Glutamate on rat brain synaptosomes of different age groups. Aging brain functions were assessed by measuring the activities of superoxide dismutase (Mn-SOD) and monoamine oxidase (MAO) and intrasynaptosomal [Ca(2+)](i )levels in presence of neuropeptides and neurotransmitters. Increase in age decreased the SOD and MAO enzyme activities; Abeta (25-35) addition further had damaging/toxic effects on the enzymes, whereas NKB alone and in combination with amyloid lowered the toxic effects caused by Abeta (25-35) addition, which was concentration (peptide) and age dependent. Oxidative stress and excitotoxicity are major consequences associated with the age, [Ca(2+)](i )was increased with the age and the neuropeptides and neurotransmitters elicited significant modulatory effects on it. Our study elucidates an increased activity of SOD, decreased activity of MAO and restoration of [Ca(2+)](i) levels in the presence of NKB and suggests an antioxidant, neuromodulatory and neuroprotective role of tachykinin peptide NKB against the beta amyloid induced toxicity.

The effect of different concentrations (0.1-5 microM) of neurokinin B (NKB) and Abeta (25-35) on acetylcholine esterase (AChE), Na(+)-K(+) ATPase and membrane fluidity (DPH anisotropy) were investigated in rat brain synaptosomes of 3, 9, 18 and 30 months old. An age dependent decrease was observed for all the three parameters studied. An in vitro incubation of isolated brain synaptosomes with Abeta (25-35) showed toxic effects on all the parameters studied and the peptide had concentration and age dependent effects, while NKB showed stimulating effect on the parameters and the combined NKB+Abeta (25-35) incubations showed a partial reversal effect as compared to the Abeta (25-35) alone. Thus, the results suggest a membrane mediated function for NKB and its role in neuromodulation, neuroprotection and antioxidant property against Abeta (25-35) induced toxicity in aging brain functions.

Oral administration of vanadate is an effective treatment for diabetes in animal models. However, vanadate exerts these effects at high doses and several toxic effects are produced. Low doses of vanadate are relatively safe but are unable to elicit any antidiabetic effect. The present study explored the prospect of using low doses of vanadate in combination with Trigonella seed powder (TSP) to evaluate their antidiabetic effect in alloxan-diabetic rats. Alloxan-diabetic rats were treated with insulin, vanadate, TSP and vanadate and TSP in combination for 3 weeks. The effect of these antidiabetic compounds was examined on general physiological parameters and distribution of glucose transporter (GLUT4) in skeletal muscle by immunoblotting and immunohistochemistry. Treatment of alloxan-diabetic rats with insulin, vanadate, TSP and vanadate in combination with TSP revived normoglycemia and restored the disturbances in the distribution of GLUT4 in skeletal muscle. TSP treatment was only partially effective in the restoration of diabetic alterations. The treatment of diabetic rats with combined doses of vanadate and TSP was most effective in the normalization of plasma glucose levels and correction of altered GLUT4 distribution.

Vanadium has been reported to have broad pharmacological activity both in vitro and in vivo. Vanadium compound, sodium orthovanadate, Na3VO4, is well known for its hypoglycaemic effects. However, Na3VO4 exerts these effects at relatively high doses (0.6 mg/ml) and exhibit several toxic effects. In the present study lower doses of Na3VO4 (0.2 mg/ml) are combined with Trigonella foenum graecum seed powder (TSP), another hypoglycaemic agent, to reduce its toxicity without compromising its antidiabetic potential. The efficacy of the lower doses of Na3VO4 has been investigated in restoring the altered glucose metabolism and histological structure in the sciatic nerves in 21 and 60 days alloxan diabetic rats. A portion of the glucose was found to be channelled from the normal glycolytic route to polyol pathway, evident by the reduced hexokinase activity and increased polyol pathway enzymes aldose reductase and sorbitol dehydrogenase activity causing accumulation of sorbitol and fructose in diabetic conditions. Ultrastructural observation of the sciatic nerve showed extensive demylination and axonal loss after eight weeks of diabetes induction. Blood glucose levels increased in diabetic rats were normalized with the lower dose of vanadium and Trigonella treatment. The treatment of the diabetic rats with vanadium and Trigonella prevented the activation of the polyol pathway and sugar accumulations. The sciatic nerves were also protected against the structural abnormalities found in diabetes with Trigonella foenum graecum as well as Na3VO4. Results suggest that lower doses of Na3VO4 may be used in combination with TSP as an efficient antidiabetic agent to effectively control the long-term complications of diabetes in tissues like peripheral nerve.

Trigonella foenum graecum seed powder (TSP) and sodium orthovanadate (SOV) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects on anti-oxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes was induced by alloxan monohydrate (15 mg/100 g body wt.) and they were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP and a combination of 0.2 mg/ml SOV with 5% TSP for 21 days. Blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Na+/K+ ATPase, membrane lipid peroxidation and fluidity were determined in different fractions of whole brain after 21 days of treatment. Diabetic rats showed high blood glucose (P less than 0.001), decreased activities of SOD, catalase and Na+/K+ ATPase (P less than 0.01, P less than 0.001 and P less than 0.01), increased levels of GPx and MDA (P less than 0.01 and P less than 0.001) and decreased membrane fluidity (P less than 0.01). Treatment with different antidiabetic compounds restored the above-altered parameters. Combined dose of Trigonella and vanadate was found to be the most effective treatment in normalizing these alterations. Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic effects.

Effects of exogenous dehydroepiendrosterone (DHEA) administration on the levels of lipid proxidation products, malondialdyde (MDA)-a thiobarbuteric acid reactive substance (TBARS) and 4-hydroxynonenal (4-HNE) in different brain regions viz. cerebral cortex, hippocampus cerebellum, and brain stem of 12 and 22 months old rats were studied. DHEA treatment significantly depressed TBARS and 4-HNE in all the brain regions studied, in both the age group rats. Interestingly, the magnitude of decrease was higher in the 22 months old rats than that in 12 months old rats. The results suggest that older the animal, better will be the response of exogenous DHEA administration against age-related peroxidative products.

In aging tissues the oxidative stress increases due to decreased activity of antioxidant enzymes and proteolysis increases due to decreased activity of aminotransferases, which can be modified by hormonal replacement therapy (HRT). The aim of the present study was to determine the effect of HRT on the activities of an antioxidant enzyme superoxide dismutase (SOD) and aminotransferases like alanine aminotransferase (Ala-AT) and aspartate aminotransferase in different age groups (12, 18 and 24 months) of naturally menopausal rats. The rats were given the subcutaneous injection of 17beta-estradiol, progesterone and combination of estradiol and progesterone for 1 month. The activity of SOD, Ala-AT and Asp-AT was measured in the brain (cerebral hemisphere, CH), heart, liver, kidney and uterus. The activity of SOD decreased with age in all the tissues taken particularly in liver. After HRT the enzyme activities were increased as compared to age-matched controls in all the tissues of aging rats. The activities of transaminases (Ala-AT and Asp-AT) showed a decrease with age in all the tissues and administration of estradiol and combination of estradiol and progesterone further decreased both the aminotransferases. Our study elucidates that increased activity of SOD contributes in protection of cells from oxygen toxicity by catalyzing the dismutation of free radicals in tissues. Furthermore, the HRT probably decreases gluconeogenesis and proteolysis by decreasing the activities of Ala-AT and Asp-AT in aging rat tissues.

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

Aging of the normal brain is accompanied by changes in its structure, function, and metabolism. There are significant gender differences in aging brain. Most of these changes increase during menopausal condition in females when the level of estradiol and progesterone are decreased. The objective of this study was to determine the effect of estradiol and progesterone (separate as well as combined) hormones in neuronal tissues from naturally menopausal rats of different age groups. Results show decreased activity of Acetylcholine esterase (AChE) whereas the level of lipid peroxidation increased with age, and after the hormone treatments both AChE activity and level of lipid peroxidation returned to control values. The deposition of lipofuscin, a pigment that accumulated intraneuronally in brain and other tissues and is considered a marker of aging, was increased with aging and the hormone treatment decreased this deposition. The present study clearly shows reduction in risk factors associated with aging in the murine model system by hormone treatments, namely estrogen and progesterone by increasing the activity of acetylcholine esterase and decreasing the levels of lipid peroxidation and lipofuscin deposition in different parts of aging brain. This study suggests that hormone replacement therapy may either reduce or delay the onset of age related diseases like Alzheimer's, Parkinson's and other neurological disorders.

Momordica charantia Linn., commonly called bitter gourd, is a medicinal plant used in the Ayurvedic system of medicine for treating various diseases including diabetes mellitus. Sodium orthovanadate (SOV) is also well-known insulin mimetic and an antidiabetic compound. Our laboratory has been using reduced doses of SOV along with administration of herbal extracts to alloxan diabetic rats and has established this combination as a good antihyperglycemic agent. The present study was undertaken to investigate the effects of treatment of Momordica fruit extract (MFE) and sodium orthovanadate, separately and in combination, on serum and tissue lipid profile and on the activities of lipogenic enzymes in alloxan induced diabetic rats. The results show that there was a significant (p < 0.01) increase in serum total lipids, triglycerides and total cholesterol levels after 21 days of alloxan diabetes. In the liver and kidney of diabetic rats the levels of total lipids and triglycerides also increased significantly (p < 0.01) while levels of total cholesterol decreased significantly (p < 0.01 and p < 0.05, respectively). The lipogenic enzymes showed decreased activity in the diabetic liver, while in kidney they showed an increased activity. When compared with the controls these changes were significant. The treatment of alloxan diabetic rats with MFE and SOV prevented these alterations and maintained all parameters near control values. Most effective prevention was however observed in a combined treatment of Momordica with a reduced dose of SOV (0.2%). The results suggest that Momordica fruit extract and SOV exhibit hypolipidemic as well as hypoglycemic effect in diabetic rats and their effect is pronounced when administered in combination.

Trigonella foenum graecum is a well-known hypoglycemic agent used in traditional Indian medicines. It was previously reported that oral administration of its seed powder for 3 weeks to alloxan diabetic rats stabilized glucose homeostasis and free radical metabolism in liver and kidney. In the present study, we further investigated the effects of 3 weeks alloxan induced diabetes on the histological structure and function of liver and kidney and the protective effect of T. foenum graecum seed powder (TSP) oral administration to the diabetic rats utilizing enzyme analysis and light and transmission electron microscopy. The activity of the enzyme, glutamate dehydrogenase was significantly higher whereas the activity of D-beta-hydroxybutyrate dehydrogenase enzyme was significantly lower in liver and kidney of alloxan-induced diabetic rats. Histopathological studies showed liver degenerative and early nephropathic changes in diabetic rats. Ultrastructure of the diabetic liver revealed a reduction in the rough endoplasmic reticulum and swelling of mitochondria in the hepatocytes. TSP treatment to the diabetic rats effectively prevented the alteration in the activities of the two enzymes and partially prevented the structural abnormalities thus suggesting a protective effect of TSP on the liver and kidney of the diabetic rats. The role of TSP in reversing the diabetic state at the cellular level besides the metabolic normalization further proves its potential as an antidiabetic agent.

Neurokinin B (NKB), a decapeptide of mammalian origin exhibits a variety of biological activities such as regulatory functions in reproduction, pre-eclampsia and neuroprotection in Alzheimer's disease. In order to gain insight into structure-function relationship, three-dimensional structure of NKB has been investigated using CD spectropolarimetry and two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy in aqueous and membrane mimetic solvents. Unambiguous NMR assignments of resonances have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments. Distance constraints obtained from the NMR data have been used to generate a family of structures, which have been refined using restrained energy minimization and dynamics. Our data show that a helical structure is induced in NKB, in presence of perdeuterated dodecyl phosphocholine (DPC) micelles, a membrane model system. Further, the conformation adopted by NKB in presence of DPC micelles represents a structural motif typical of neurokinin-3 selective agonists.

The natural mutations observed in pyruvate kinase (PK)-M2, a homotetramer isozyme, in this study correlated with the differential activity of the enzyme in a dominant negative manner in B-lymphoblastoid cells, established from two Bloom syndrome (BS) patients, BS1 and BS3 by 50 and 90%, respectively; and by 75% in the freshly obtained PHA stimulated lymphocytes of a BS patient diagnosed for the first time in India. A gene screen involving the critical domains of the PK-M gene in BS cells resulted in the observation of a missense mutation in BS1 and the BS patient and a frame shift mutation in BS3, in exon-10, coding for the intersubunit contact domain (ISCD) of the PK-M2 protein. Apart from these mutations, other variations in this region of the gene, both in normal and BS cells, did not affect the enzyme activity, since these were silent. Computer-based modeling studies of the PK-M2 protein with each mutation was suggestive of a changed interaction between two domains within a subunit in BS1, a gross structural change in BS3, and a changed interaction between two subunits of the tetramer in the BS patient. An absence of such mutations in other regions of the PK-M2 gene in normal subjects and in the randomly chosen unrelated genes in the DNA from BS cell lines and the cells from the BS patient, authenticated the presence of the observed mutations in Bloom syndrome cells. A correlation observed between the differential enzyme activity and the nature of mutation in the intersubunit contact domain (ISCD) region of the PK-M2 gene was interesting, and indicted how the site and the nature of mutation in a heterozygous state could influence the enzyme activity differentially and in a dominant negative manner. The importance of these mutations in Bloom syndrome cells, however, remains to be elucidated, and can only be conjectured.

Background: Vanadate treatment to diabetic rats has been reported to correct the altered carbohydrate metabolism and antioxidant status. However, vanadate exerts these effects at relatively high doses and several toxic effects are produced. We used low doses of vanadate in combination with Trigonella foenum graecum seed powder (TSP) and evaluated their effect on the enzyme changes in diabetic rats., Methods: Alloxan-diabetic rats were treated separately with insulin, vanadate (0.6 mg/ml), TSP and a combined dose of Vanadate (0.2 mg/ml) and TSP for 21 days. At the end of the experimental period, blood glucose levels and activities of pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were measured in cytosolic fraction in the liver and kidney., Results: Blood glucose levels increased markedly in diabetic rats. Treatment with antidiabetic compounds resulted in the reduction of glucose levels. Rats treated with combined dose of vanadate and trigonella had glucose levels comparable to control ones. Similar results were obtained with the activities of PK, PEPCK, SOD, GPx, GR, and CAT in liver and kidney of diabetic rats. Combined dose of vanadate and Trigonella was found to be most effective in correcting these alterations., Conclusions: Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic side effects.

The reticulocytes and the ageing red blood cells (RBCs) namely young (Y), middle-aged (M) and old RBCs (O) of female Wistar rats from different groups such as control animals (C), controls treated with vanadate (C + V), alloxan-induced diabetic (D), diabetic-treated with insulin (D + I) and vanadate (D + V), were fractionated on a percoll/BSA gradient. The following enzymes were measured - hexokinase (HK), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione-s-transferase (GST), alanine aminotransferase (AlaAT), aspartate aminotransferase (AsAT) and arginase in the hemolysates of all the RBCs fractions. Decreases in the activity of HK and AsAT by about 70%, arginase and GSH-Px by 30% in old RBCs were observed in comparison to reticulocytes of control animals. Increases in the activity of GSSG-R by 86%, AlaAT by more than 400% and GST by 70% were observed in old RBCs in comparison to reticulocytes of control animals. Alloxan diabetic animals showed a further decrease in the activities of HK in Y RBCs by 37%, M RBCs by 39% and O RBCs by 32%, GSH-Px activity in Y RBCs by 13%, M RBCs by 20% and O RBCs by 33% and GST activity in Y RBCs by 14%, M RBCs by 42% and O RBCs by 60% in comparison to their corresponding cells of control animals. An increase in the activity of all the enzymes studied was also observed in reticulocytes of diabetic animals in comparison to reticulocytes of controls. The GSSG-R activity was found to be increased in Y RBCs by 49%, M RBCs by 67% and O RBCs by 64% as compared to the corresponding age-matched cells of control animals. The activity of arginase also decreased in Y RBCs by about10%, M RBCs by 20% and O RBCs by 30% in comparison to the age-matched cells of control animals. A decrease in the activity of AsAT in Y and M RBCs by 30%, and O RBCs by 25% was observed in diabetic animals in comparison to the age-matched cells of control animals. The activity of AlaAT was found to be decreased by more than 10% in Y and M RBCs and 25% in O RBCs of diabetic animals in comparison to the age-matched cells of control animals. Insulin administration to diabetic animals reversed the altered enzyme activity to control values. Vanadate treatment also reversed the enzyme levels except for that of GST in old cells.

Sodium-orthovanadate (SOV) and seed powder of Trigonella foenum graecum Linn. (common name: fenugreek, family: Fabaceae) (TSP) besides being potential hypoglycemic agents have also been shown to ameliorate altered lipid metabolism during diabetes. This study evaluates the short-term effect of oral administration of SOV and TSP separately and in concert (for 21 days) on total lipid profile and lipogenic enzymes in tissues of alloxan diabetic rats. Diabetic rats showed 4-fold increase in blood glucose. The level of total lipids, triglycerides and total cholesterol in blood serum increased significantly during diabetes. During diabetes the level of total lipids increased significantly (P < 0.001) in liver and in kidney by 48% and 55%, respectively, compared to control. Triglycerides level increased by 32% (P < 0.01) in liver and by 51% (P < 0.005) in kidney, respectively, compared to control. Total cholesterol level also increased significantly in both liver and kidney (P < 0.01 and P < 0.001, respectively). The activities of NADP-linked enzymes; namely glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and the activities of lipogenic enzymes namely ATP-citrate lyase (ATP-CL) and fatty acid synthase (FAS) were decreased significantly in liver and increased in kidney during diabetes as compared to control. SOV and TSP administration to diabetic animals prevented the development of hyperglycemia and alteration in lipid profile in plasma and tissues and maintained it near normal. Maximum prevention was observed in the combined treatment with lower dose of SOV (0.2%) after 21 days. We are presenting for the first time effectiveness of combined treatment of SOV and TSP in amelioration of altered lipid metabolism during experimental type-I diabetes.

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.

The aim of this study was to determine the effect of administration of estradiol (E2), progesterone (P4), and combination of estradiol and progesterone (EP) in aging female rats. The changes in the activities of hexokinase (HK), glucose-6-phosphatase (G6P'tase) and glucose-6-phosphate dehydrogenase (G6PDH) enzymes, and in protein levels in tissues of rats namely brain (cerebral hemisphere), heart, liver, kidney and uterus have been measured in different age groups. The random blood sugar level was measured in serum and liver. The different age groups of rats were given 0.1 microg/g body weight estradiol, 2.5 microg/g body weight progesterone and a similar concentration of both in a combined treatment for 1 month. This dose was selected after determining estrogen and progesterone levels in 3 month adult female animals so that the aging female animals had circulating hormone levels nearly the same as those of young female animals. The random sugar level was determined in serum and liver cytosolic fractions, and it was increased by combination treatment. The protein content in tissues showed significant changes only with combined hormone administration when compared with age-matched controls. The activity of HK decreased in aged animals and significantly increased by hormone treatments in all the tissues of the aged rats studied. The activity of G6P'tase increased with age up to 1.5 years and decreased in 2 years. Treatment with E2 and EP further decreased the activity significantly in all the tissues. G6PDH showed a similar pattern as was observed in HK in all the age groups. Therefore, the E2 and EP treatments caused an entire series of growth-related responses, including an increased uptake of glucose, increased the protein level in the tissues of aging rats, thereby reducing the risk factors associated with aging by normalizing hormone levels which decreased with aging and resulted in diseases such as Alzheimer's diseases and diabetes.

The effect of estradiol and progesterone therapy in serum and liver on the lipid profile of naturally menopausal albino rats of the Wistar strain of different age groups (12,18 and 24 months) have been measured and compared with the age matched groups. Three months old rats were used as young controls. The aged rats were administered subcutaneous injection of 17-beta-estradiol (0.1 microg/g body weight), progesterone (2.5 microg/g body weight) and similar concentrations of both in combined treatment for 1 month and the level of triglycerides (TG), total lipids (TL), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were measured in serum and liver of 3, 12, 18 and 24 months old control as well as treated groups. The results show that TG, HDL, VLDL levels were increased significantly by 71%, 155%, 54%, respectively in liver of 24 months old rats by combination treatment when compared with age matched control animals. The levels of TL, TC and LDL were decreased by 20%, 31%, and 30%, respectively in serum of 12 months old rats in combination treatment group. The effect was more significant in 12 and 24 months old female rats with administration of estrogen and combined (EP) treatments. The results indirectly suggest that hormone replacement therapy (HRT) can reduce the risk of cardiovascular disease (CVD) thereby playing a cardio-protective role by restoring lipid and hormone levels to the similar levels as found in young female animals.

The effect of oral administration of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP), a medicinal plant used extensively in Asia, on the mitochondrial metabolism in the alloxan diabetic rats has been investigated. Rats were injected with alloxan monohydrate (20 mg/100 g body wt) or vehicle (Na-acetate buffer), the former were treated with either 2 IU insulin i.p., 0.6 mg/ml SOV ad libitum, 5% TSP ad libitum, and a combination of 0.2% SOV and 5% TSP ad libitum for 21 days. Selected rate-limiting enzymes of the tricarboxylic acid cycle, hydrogen shuttle system, ketone body metabolism, amino acid metabolism and urea cycle were measured in the mitochondrial and cytosolic fractions of liver, kidney and brain tissues of the experimental rats. Majority of the mitochondrial enzymes in the tissues of the diabetic rats had significantly higher activities compared to the control rats. Similarly, the activities of mitochondrial and cytosolic aminotransferases and arginase were significantly higher in liver and kidney tissues of the diabetic rats. The separate administrations of SOV and TSP to diabetic rats were able to restore the activities of these enzymes to control values. The lower dose of SOV (0.2%) administered in combination with TSP to diabetic rats lowered the enzyme activities more significantly than when given in a higher dose (0.6%) separately. This is the first report of the effective combined action of oral SOV and TSP in ameliorating the altered mitochondrial enzyme activities during experimental type-1 diabetes. Our novel combined oral administration of SOV and TSP to diabetic rats thus conclusively proves as a possible method to minimize potential vanadate toxicity without compromising its positive effects in the therapy of experimental type-1 diabetes.

In order to evaluate the modulatory effects of manganese, high fat diet fed and alloxan diabetic rats were taken and the changes in the glucose oxidation, glycerol release and effects of manganese on these parameters were measured from adipose tissue. An insulin-mimetic effect of manganese was observed in the adipose tissue in the controls and an additive effect of insulin and manganese on glucose oxidation was seen when Mn2+ was added in vitro. The flux of glucose through the pentose phosphate pathway and glycolysis was significantly decreased in high fat fed animals. Although the in vitro addition of Mn2+ was additive with insulin when 14CO2 was measured from control animals, it was found neither in young diabetic animals (6-8 weeks old) nor in the old (16 weeks old). Both insulin and manganese caused an increased oxidation of carbon-1 of glucose and an increase of its incorporation into 14C-lipids in the young control animals; the additive effect of insulin and manganese suggests separate site of action. This effect was decreased in fat fed animals, diabetic animals and old animals. Manganese alone was found to decrease glycerol in both the control and diabetic adipose tissue in in vitro incubations. The results of the effects of glucose oxidation, lipogenesis, and glycerol release in adipose tissue of control and diabetic animals of different ages are presented together with the effect of manganese on adipose tissue from high fat milk diet fed animals.

With the premise that oxygen free radicals may be responsible for the severity and complications of diabetes, the level of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as the oxidative damage were examined in the tissues of control, diabetic and treated rats. After 3 weeks of diabetes, the activity of CAT was significantly increased in heart in diabetes (about 6-fold) but decreased in liver. The SOD activity decreased significantly in liver but increased in brain. The activity of GPx decreased significantly in liver and increased in kidney. A significant increase was observed in oxidative damage in heart and kidney and a small increase in brain with decrease in liver and muscle. Vanadate and fenugreek (Trigonella foenum graecum) administration to diabetic animals showed a reversal of the disturbed antioxidant levels and peroxidative damage. Results suggest that oxidative stress play a key role in the complications of diabetes. Vanadate and fenugreek seeds showed an encouraging antioxidant property and can be valuable candidates in the treatment of the reversal of the complications of diabetes.

Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADP-linked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4-fold higher blood glucose level and a 0.7-fold lower body weight compared to normal controls. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities of gluconeogenic enzymes were higher in both liver and kidney during diabetes, however the activities of the lipogenic enzymes were decreased in both tissues during diabetes. Trigonella seed powder treatment to diabetic rats for 21 days brought down the elevated fasting blood glucose levels to control levels. The altered enzyme activities were significantly restored to control values in both the liver and kidney after Trigonella seed powder treatment. The therapeutic role of Trigonella seed powder in type-1 diabetes as exemplified in this study can be attributed to the change of glucose and lipid metabolising enzyme activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney. These biochemical effects exerted by Trigonella seeds make it a possible new therapeutic in type-1 diabetes.

The main purpose of this study was to investigate the effect of free radicals and experimental diabetes on cytosolic creatine kinase activity in rat heart, muscle and brain. Hydrogen peroxide decreased creatine kinase activity in a dose dependent manner which was reversed by catalase. Xanthine/xanthine oxidase, which produces superoxide anion, lowered the creatine kinase activity in the same manner whose effect was protected by superoxide dismutase. N-acetylcysteine and dithiothreitol also significantly ameliorated the effect of Xanthine/xanthine oxidase and hydrogen peroxide. Experimental diabetes of twenty-one days (induced by alloxan), also caused a similar decrease in the activity of creatine kinase. This led us to the conclusion that the decrease in creatine kinase activity during diabetes could be due to the production of reactive oxygen species. The free radical effect could be on the sulfhydryl groups of the enzyme at the active sites, since addition of sulfhydryl groups like N-acetylcysteine and dithiothreitol showed a significant reversal effect.

Administration of sodium orthovanadate to diabetic animals exhibits insulin-like effects and has been effective in the reversal of biochemical complications. This study evaluates the effect of sodium orthovanadate (0.6 mg/ml) treatment for 21 days on the hepatic glucose homeostasis and lipid metabolism in alloxan diabetic rats. The activities of two lipogenic enzymes, glucose-6-phosphate dehydrogenase and malic enzyme; and related enzymes, hexokinase and glucose-6-phosphatase were measured in the liver cytosolic fractions of diabetic rats and diabetic rats treated separately with insulin and sodium orthovanadate. The total lipids, triglycerides and cholesterol levels were estimated in the livers of the diabetic and the treated rats. The activities of both the lipogenic enzymes and hexokinase isozymes were significantly decreased, whereas the activity of glucose-6-phosphatase was significantly increased in the diabetic liver. During diabetes, the levels of total lipids and triglycerides increased significantly with a decrease in the cholesterol levels in the liver. Insulin and vanadate were able to restore the altered enzyme activities to almost control levels. Both insulin and vanadate were found to partially restore the altered levels of total lipids, triglycerides and cholesterol in the livers of diabetic rats. The results indicate that vanadate administration to diabetic animals normalizes blood glucose and causes marked improvement of altered lipid metabolism during diabetes. The present study and earlier reports suggest the possible use of vanadate as insulin replacement in the therapy of diabetes when administered at pharmacological doses.

This work was carried out to study the effects of vanadate on the expression of liver-type arginase in experimentally induced diabetes in the rat. The results showed that the activity and mRNA levels of arginase were increased significantly in the diabetic condition. Vanadate treatment reversed the increased activity and restored mRNA levels of arginase almost to the control values. The reversal effects of vanadate were found to be similar to those of insulin, and this further confirms the insulin-like effects of vanadate. ELISA and slot-blot assay observations were consistent with the biochemical measurements of enzyme activity. The increase in arginase activity and mRNA levels in diabetes and the decrease in insulin- and vanadate-treated animals may be due to the transcriptional regulation of arginase.

This work was carried out to study the modulation of arginase expression in experimental diabetes. Here, we have demonstrated that liver arginase activity and mRNA levels increased significantly in diabetic condition. Insulin treatment reverses the increased activity and mRNA levels nearly to the control values. The reversal effects of vanadate are found to be similar to that of insulin and this observation further reiterates the insulin-like effects of vanadate. ELISA and slot blot assay observations are consistent with biochemical measurements of enzyme activity. These results show an increase in arginase activity and mRNA levels in diabetes and decrease in treated animals may be due to the transcriptional regulation of arginase gene.

The in vivo effects of insulin, and other insulino mimetic agents like vanadate and fenugreek (T. foenum graecum) were followed on the changes in the activities of creatine kinase in heart, skeletal muscle and liver of experimental diabetic rats. As compared to control rats, creatine kinase activities were found to decrease significantly in the tissues during experimental diabetes. All the antidiabetic compounds used namely, insulin, vanadate and Fenugreek seed powder normalised the decreased activities to almost control values. The effects of insulin and vanadate were comparable in restoring normoglycemia and the creatine kinase activities.

The effects of insulin, sodium orthovanadate and a hypoglycemic plant material, Trigonella foenum graecum (fenugreek) seed powder were studied on the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in diabetic liver and kidney. The significantly increased activities of the two enzymes during diabetes in liver and kidney were found to be lowered to almost control values by the use of the antidiabetic compounds. Diabetic liver exhibited a much greater increase in the activities of the two enzymes than diabetic kidney. The highest percentage of reversal to normal values was seen using the combination of vanadate and Trigonella seed powder. The lowered rate of growth of the animals as well as the increased blood sugar were reversed almost to the control levels by the Trigonella seed powder and vanadate treatment. The inclusion of the Trigonella seed powder overcame the toxicity of vanadium encountered when it was given alone as insulin mimetic agent. Much lower levels of vanadate were needed when it was given in combination with Trigonella seed powder. Their combined effects were better at restoring the above parameters than those induced by insulin administration.

The activity of glyoxalase I from the soluble fraction of diabetic rat liver was found to decrease as compared to the control. Sodium orthovanadate in drinking water and Trigonella foenum graecum seed powder when administered to these diabetic animals were found to reverse the activity of glyoxalase I to control values. A combination of the above two antidiabetic compounds showed a better reversal. Vanadate and Trigonella seed powder treatment separately to diabetic rats also normalized hyperglycemia together with glyoxalase I activity. A combination of vanadate and Trigonella seed powder also restored the other general parameters of the diabetic animals.

Experimentally induced diabetic rats were treated separately with insulin and vanadate. The activities of hexokinase (HK) and glucose-6-phosphate dehydrogenase (G-6PDH) were increased in reticulocyte hemolysate isolated from the diabetic rats and were restored to normal levels by insulin. The restoration was not detected in vanadate treated diabetic animals. The enzymes of glutathione metabolism namely glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-s-transferase (GST) exhibited increases in their activities with diabetes and were restored to almost control values by insulin treatment. Vanadate given to diabetic animals further increased GPx, and GST. The level of superoxide dismutase(SOD) decreased in the reticulocytes of diabetic rats and catalase (CAT) was unchanged. Both CAT and SOD had normal values when the diabetic rats were treated with insulin and vanadate. It is proposed that vanadate may cause an increase in the activity of GR which may stimulate glucose transporters and glucose metabolism.

Diabetes has been classified as a disease of glucose overproduction by tissues, mainly liver and glucose underutilization by insulin requiring tissues like liver, adipose and muscle due to lack of insulin. There is, however, glucose over utilization in tissues not dependent on insulin for glucose transport like kidney, nerve and brain. There are serious complications due to this excess glucose in these tissues and their reversal is important for a good metabolic control and normalisation of other parameters. Insulin, trace metals and some plant extracts have been used to see the reversal effects of the complications of diabetes in liver and kidney in experimental diabetes. Almost complete reversal of the metabolic changes has been achieved in the activities of key enzymes of metabolic pathways in liver and kidney and an effective glucose control has been achieved suggesting a combination of therapies in the treatment of metabolic disturbance of the diabetic state.