Biomedical subjects

Jitsuya Takada

Publications and source records attributed to Jitsuya Takada.

6 recordsLinked to original sources

PubMed2006

Bis(allixinato)oxovanadium(IV) complex is a potent antidiabetic agent: studies on structure-activity relationship for a series of hydroxypyrone-vanadium complexes.

There is an urgent medical need for orally effective drugs to replace insulin injections for the treatment of diabetes mellitus. Vanadium complexes with insulin-mimetic activities have recently been proposed as candidates as new antidiabetic drugs. Following in vitro and in vivo studies on a group of bis(3-hydroxy-4-pyronato)oxovanadium(IV) (1) complexes with VO(O4) coordination mode, bis(allixinato)oxovanadium(IV) (3) which contains allixin, a garlic component, was found to be the most potent antidiabetic agent among them. Complex 3 with a high in vitro insulin-mimetic activity in terms of both free fatty acid (FFA)-release inhibitory and glucose-uptake enhancing activities in isolated rat adipocytes exhibited a high hypoglycemic effect in type 1 diabetic model mice by both intraperitoneal injections and oral administrations. Complex 3 is thus proposed to be one of the most effective candidates for antidiabetic therapy.

Adipocytes↗

PubMed2006

Improvement of diabetes, obesity and hypertension in type 2 diabetic KKAy mice by bis(allixinato)oxovanadium(IV) complex.

Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx)(2)) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx)(2) was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx)(2) was examined in obesity-linked type 2 diabetic KKA(y) mice. Treatment of VO(alx)(2) for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA(y) mice; however, it had no effect on hypoadiponectinemia. VO(alx)(2) also improved hyperleptinemia, following attenuation of obesity in KKA(y) mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx)(2) is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.

Animals↗

PubMed2006

Memory deficit in mice administered aluminum-maltolate complex.

Recently, aluminum (Al) has been identified as one of the environmental factors responsible for cause certain nerve degeneration diseases, particularly, Alzheimer's disease (AD). However, the relationship between Al and AD is controversial. We previously examined whether Al induced neurotoxin in the brain of mice when aluminum-maltolate complex (ALM) was administered daily for 120 days. Our results revealed that Al accumulated in the brain induced oxidative stress, and the nerve degeneration was detected in the brain of the ALM-treated group. On the basis of these results, we have tried to examine whether the incorporated Al affects memory in mice with regard to an indicator of spatial memory deficits depending on the chemical forms of Al, namely, as an ion (AlCl3) and in the form of a complex (ALM). We administered saline, AlCl3, and ALM at a concentration of 40 micromol Al/kg body weight to mice by daily ip injections for 60 days. We assessed spatial memory by a water maze task and determined the Al levels in the brain of the mice by the neutron activation analysis method. Spatial memory deficit as an indicator of the swimming time was related to Al accumulation in the brain of mice; the chemical form of the Al compound was important in order to exhibit the memory deficit in mice; the uptake of Al is higher in mice when it is administered in a complex form than in an ionic form.

Animals↗

PubMed2005

Characterization of a novel Na+/H+ antiporter gene InNHX2 and comparison of InNHX2 with InNHX1, which is responsible for blue flower coloration by increasing the vacuolar pH in the Japanese morning glory.

The reddish-purple buds of the wild-type Japanese morning glory (Ipomoea nil) change into blue open flowers, and the shift in the flower coloration correlates with an increase in the vacuolar pH of the flower epidermal cell. In the mutant deficient in the InNHX1 gene for the vacuolar Na(+)/H(+) antiporter, the vacuolar alkalization occurs only partially, and reddish-purple buds become purple open flowers. While most of the plant NHX genes characterized are generally expressed in leaves, stems and roots and induced by NaCl treatment, the InNHX1 gene is expressed predominantly in the flower limbs at around 12 h before flower opening. It is expressed very sparsly in leaves, stems and roots, and no induction occurs in response to NaCl treatment. Here, we identified a novel vacuolar Na(+)/H(+) antiporter gene InNHX2, which is expressed in leaves, stems and roots and is induced in response to NaCl treatment. In addition, relatively higher expression of InNHX2 was observed in the flower limbs shortly before flower opening. We also discovered that both the InNHX1 and InNHX2 proteins can catalyze both Na(+) and K(+) transport into vacuoles. These results suggest that InNHX2 performs dual functions: to confer salt tolerance on the plant and to promote partial vacuolar alkalization in the petals. The implication is that the InNHX2 protein is probably one of the components responsible for converting reddish-purple buds into purple open flowers by partially increasing the vacuolar pH in the absence of major InNHX1 activity.

Amino Acid Sequence↗

PubMed2004

A new candidate for insulinomimetic vanadium complex: synergism of oxovanadium(IV)porphyrin and sodium ascorbate.

Vanadyl-meso-tetrakis(1-methylpyridinium-4-yl)porphyrin, VOTMpyP with the VO(N(4)) coordination mode, was found to have a potent insulinomimetic activity on the basis of in vitro and in vivo experiments. When the complex was given simultaneously with sodium ascorbate, the high blood glucose levels of type 1 diabetic model STZ-rats were lowered by synergistic effect, probably sustaining the vanadyl state by means of ascorbate distributed in the organs and tissues of animals. This is the first finding on not only the insulinomimetic vanadyl-porphyrin complex but also the occurrence of a synergistic effect of VOTMpyP and sodium ascorbate to lower the high blood glucose levels in diabetic animals.

Animals↗

PubMed2004

Orally administrated aluminum-maltolate complex enhances oxidative stress in the organs of mice.

Recently, aluminum (Al) in drinking water has been proposed to be a risk factor for development of Alzheimer's disease (AD). Because the physiological role of Al in humans is not yet known, we previously examined this role using an experimental animal model. Our results revealed a greater accumulation of Al in the brain, liver, kidney and spleen of mice who received long-term (90 days) administration of an Al complex, aluminum-maltolate (ALM), than in untreated controls. This observation prompted us to examine the degree of injury in the organs of mice in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances (TBARS) and NOx levels in order to determine the effects of Al accumulation. Six-week-old mice were given drinking water containing AlCl3 or ALM for 120 days. TBARS and NOx levels were found to change depending on the organs and chemical forms of Al. In particular, TBARS and NOx levels in the brain of mice given ALM for 30, 60 and 120 days were significantly increased compared with those of the control group. In addition, nervous degeneration was detected in the brain of the ALM-treated group. These results indicate that the chemical form of Al alters the distribution and oxidative stress in the brain. In addition, we propose a more precise method of determining Al levels in biological systems using neutron activation analysis. When the biological samples are irradiated with a neutron flux, both 27Al and 31P can be counted to 28Al by the reactions, 27Al(n,gamma)28Al and 31P(n,alpha)28Al, respectively. The level of Al in the organs can then be determined by subtraction of the radioactivity due to 28Al originated in 31P from the total radioactivity of the samples.

Administration, Oral↗