A newly synthesised molybdenum/ascorbic acid complex alleviates some effects of cardiomyopathy in streptozocin-induced diabetic rats.

BACKGROUND: Exogenous insulin does not prevent cardiac failure in patients with type 1 diabetes mellitus and a cardioprotective insulin mimic is greatly needed. Certain transition metals are known to act as insulin mimics and may be cardio- protective. In this study, the ability of a newly synthesised molybdenum/ascorbic acid complex to strengthen cardiac function was investigated. METHODS AND DESIGN: Male CD rats were assigned to one of five groups: non-diabetic control, non-diabetic control treated with molybdenum/ascorbic acid complex, diabetic treated with sodium ascorbate, diabetic treated with molybdenum/ascorbic acid complex and untreated diabetics. Type 1 diabetes was induced by streptozocin injection. Once diabetes was confirmed, treatment was initiated by adding either the molybdenum/ascorbic acid complex or sodium ascorbate to the drinking water and continued for 6 weeks. Following the treatment period, the animals were terminated, and their hearts were excised and mounted in a working heart perfusion apparatus. Blood samples were taken for plasma glucose and plasma lipid level determination. Cardiac function was evaluated using 1 hour of low-flow ischaemic stress followed by 30 minutes of reperfusion. RESULTS: Hearts from the animals treated with the molybdenum/ascorbic acid complex displayed the best aerobic performance of all the diabetic animals. Blood glucose levels and blood lipid levels were significantly lower in animals treated with the complex than in other diabetic animals. The group treated with the complex also had a lower drinking rate than the other diabetic groups. Furthermore, hearts from animals treated with the molybdenum/ascorbic acid complex showed a greater degree of recovery from low-flow ischaemia than any other group. CONCLUSIONS: The molybdenum/ascorbic acid complex showed some significant insulin-mimic and cardioprotective effects. Further development of this complex could provide a drug useful for alleviating some of the cardiovascular problems associated with diabetes mellitus.

Gut transport of a molybdenum/ascorbic acid complex.

BACKGROUND: Relatively little work has been done on the absorption of trace elements in the mammalian small intestine. Recently, studies have demonstrated that a molybdenum/ascorbic acid complex has shown some promise as a potentially orally administered insulin-mimetic agent. However, the transport mechanism of the molybdenum/ascorbic acid complex is unknown. In this study we examine some aspects of the movement of the complex across the intestinal wall using measurements of elemental molybdenum as an indicator because it is not possible to measure the complex directly. METHODS: Everted rat small intestine sacs were used to determine some aspects of the transport of the complex across the intestine. Intestinal sacs from five rats were incubated in a medium containing 1 g/L of the molybdenum complex. Sacs from a further five rats had 1 mmol/L of 2,4-dinitrophenol, a known inhibitor of oxidative phosphorylation, added to the incubation medium. In a second experiment, everted sacs from five rats were also incubated in media containing one of six concentrations of the molybdenum complex (0.5, 1, 2, 4, 8 or 10 g/L). RESULTS: There was no significant difference between transport rates of groups with or without 2,4-dinitrophenol in the incubation medium, suggesting that the predominant mechanism of molybdenum transport is energy-independent. There was a significant positive, linear increase in the transport rate with increasing concentration of the molybdenum complex. CONCLUSION: These data suggest that the predominant mechanism of this molybdenum/ascorbic acid complex transport in the small intestine is non-saturable and therefore not protein-mediated.

A fluorescent compound for glucose uptake measurements in isolated rat cardiomyocytes.

A focus of current diabetes research is the development of insulinomimetic compounds for oral treatment of diabetes and its associated cardiac complications. Screening compounds for their potential insulinomimetic effects usually involves the use of radioactive isotopes. The focus of this study was to investigate a nonradioactive fluorescent compound for its use in screening insulinomimetic compounds. The indicator 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) has been used by some workers to measure glucose uptake in Escherichia coli and Candida albicans. We propose that 2-NBDG will also be a suitable indicator for mammalian cell lines, in particular rat cardiomyocytes. We found that the indicator could give a reliable reproducible standard curve following appropriate dilution and is taken up by isolated cardiomyocytes. The insulinomimetic compounds vanadyl sulfate and sodium molybdate showed rates of glucose uptake similar to that of insulin. Furthermore, the rate of uptake measured for insulin using this technique (0.04 +/- 0.003 nmol x min(-1) x 10(6) cells(-1) is comparable with previous literature using 2-deoxyglucose uptake measurements on isolated myocytes (0.040 nmol x min(-1) x 10(6) cells(-1), demonstrating the validity of this fluorescent compound for glucose uptake studies.