Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan-induced diabetic rats
Introduction
Diabetes mellitus results from the destruction of the insulin-producing beta cells of the pancreas, a disease development process that can last several years before the clinical onset of the disease [1]. Mitochondria are the most important intracellular source and target of reactive oxygen species. Mitochondrial dysfunction due to enhanced free radical production has been demonstrated in various pathological conditions including diabetes mellitus [2]. Environmental factors such as poor nutrition (high fat diet) or lower oxygen consumption i.e. (VO2max) or both also seem to have a major effect on the development of peripheral insulin resistance [3]. Diabetes mellitus is associated with a reduced capacity of the β-cells to release sufficient insulin to cover demand, whether the cells are destroyed as in insulin dependent diabetes mellitus (IDDM) or intact as in non-insulin dependent diabetes mellitus (NIDDM). Elevation in the level of non-esterified fatty acids also stimulates gluconeogenesis in the liver [4]. During IDDM, decrease in the insulin : glucagon ratio leads to an increase in both glycogenolysis and gluconeogenesis [5].
The normal beta cell, highly dependent on mitochondrial energy - is the only cell, which increases its function (energy production) during hyperglycemia. During diabetic condition, the activity of the enzyme glucokinase is found to be decreased due to defective insulin release. This inturn affects phosphorylation, the first step in glycolysis which is glucokinase dependent [6]. Thus, glucokinase mutations can directly impair glucose sensing, while mitochondrial DNA mutations can indirectly impair glucose sensing by reducing intracellular concentrations of ATP [7]. Oxidation of glucosederived acetyl residues increases in a time related and concentration dependent manner when islet or purified β-cells are exposed to a rise in hexose concentration. It was proposed that the increased oxidation of glucose derived acetyl residues is attributed to Ca2+ dependent activation of NAD-isocitrate dehydrogenase and α-ketoglutarate dehydrogenase [8].
Recently trace elements like vanadium and tungsten have been shown to exhibit insulin like properties [9]. Evidence has also been presented to show that molybdenum could affect glucose metabolism in vitro [10]. Hence, an earnest attempt has been made in the present study to evaluate the effects of molybdate in correcting the diabetes-associated alterations in carbohydrate metabolizing and mitochondrial enzymes.
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Materials and methods
Male albino rats weighing between 160–180g were procured from the Veterinary College, Tamilnadu Veterinary University, Chennai, India. The animals were divided into four groups namely: Group I: control, Group II: normal rats orally administered with sodium molybdate (100mg/kg body weight/day) for 30 days, Group III: alloxan-induced animals (140mg/kg body weight intraperitoneally) were considered as diabetic when the fasting blood glucose level showed above 200mg/dl. The blood glucose levels
Statistical analysis
Values are expressed as mean ± SD for six rats in each group and significance of the differences between mean values were determined by one-way analysis of variance (ANOVA) coupled with Student-Newman-Kuel multiple comparison test. Values of p < 0.05 were considered to be significant.
Statistical significance of differences between the control (Group III) and diabetic rats (Group IV) was determined by Student’s t-test. The levels of significance were evaluated with p values.
Results
Table 1 shows the activities of carbohydrate metabolizing enzymes and the level of blood glucose (fasting blood) and glycogen in the liver of control, diabetic and molybdate treated diabetic rats. The activities of enzymes hexokinase, G6PDH, glycogen synthase and the level of glycogen were found to be low (p < 0.001) whereas the activities of enzymes aldolase, glucose-6-phosphatase, fructose 1,6-bisphosphatase and glycogen phosphorylase were found to be significantly increased (p < 0.001) in
Discussion
The activities of insulin dependent enzymes like aldolase, hexokinase, glycogen synthase and glucose-6-phosphate dehydrogenase were found to be lowered in the diabetic tissues whereas following molybdate treatment the activities of these enzymes increased in a significant manner. The activities of enzymes catalyzing insulin independent pathways are grossly increased in the untreated diabetic and are reversed during the administration of the drug. The enzymes of the group, which have been
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