Biomedical subjects

Hiromu Sakurai

Publications and source records attributed to Hiromu Sakurai.

At least 19 recordsLinked to original sources

PubMed2005

Possible mode of action for insulinomimetic activity of vanadyl(IV) compounds in adipocytes.

Vanadyl(IV) ions (+4 oxidation state of vanadium) and their complexes have been shown to have in vitro insulinomimetic activity and to be effective in treating animals with diabetes mellitus. Although, researchers have proposed many vanadyl compounds for the treatment of diabetes patients, the mode of action of vanadyl compounds remains controversial. In order to evaluate the mode of action of these compounds, we examined the insulinomimetic activity of VOSO4, bis(picolinato)oxovanadyl(IV), and bis(maltolato)oxovanadyl(IV) in the presence of several inhibitors relevant to the glucose metabolism. After confirming that these vanadyl compounds were incorporated in the adipocytes as estimated by ESR method, we evaluated the mode of action by examining free fatty acids (FFA) release in the adipocytes. Inhibition of FFA release by these vanadyl compounds was found to be reversed by the addition of inhibitors, typically by cytochalasin B (glucose transporter 4 (GLUT4) inhibitor), cilostamide (phosphodiesterase inhibitor), HNMPA-(AM)3 (tyrosine kinase inhibitor), and wortmannin (PI3-k inhibitor), indicating that these compounds affect primarily GLUT4 and phosphodiesterase, as named "ensemble mechanism". Based on these results, we suggest that vanadyl compounds act on at least four sites relevant to the glucose metabolism, and on GLUT4 and phosphodiesterase in particular in rat adipocytes, which in turn normalizes the blood glucose levels of diabetic animals. The obtained results provide evidence for the role of vanadyl ion and its complexes in stimulation of the uptake and degeneration of glucose.

Adipocytes↗

PubMed2005

Effect of insulin-mimetic vanadyl sulfate on cytochrome P450 2E1-dependent p-nitrophenol hydroxylation in the liver microsomes of streptozotocin-induced type 1 diabetic rats.

CYP2E1 is known to be induced in streptozotocin (STZ)-treated diabetic rats (STZ rats), and its induction is improved by insulin. We have examined the age-dependent changes of CYP2E1 in the liver microsomes of type 1 diabetic STZ rats, the effects of VOSO4 on the contents of total P450 and CYP2E1, and the activities of CYP2E1 in terms of p-nitrophenol hydroxylation. The contents of P450 and CYP2E1 and CYP2E1 activity were enhanced with the development of diabetes. When the hyperglycemia of STZ rats was improved by daily intraperitoneal injections of VOSO4 for 10 days at the doses of 7 mg/kg body weight for 5 days, 5 mg/kg for the following 3 days, and then 2.5 mg/kg for 2 days, the P450 and CYP2E1 levels and CYP2E1 activity were lowered than those in the untreated STZ rats. To understand the mechanism underlying CYP2E1-dependent hydroxylation activity, the production of reactive oxygen species was examined in the NADPH-liver microsomal systems by ESR spin-trapping. Singlet oxygen (1O2) was detected in all microsomal systems, while superoxide anion radical(*O2-) and hydroxyl radical (*OH) were not. On the basis of these results, we conclude that (1) CYP2E1 level and activity are enhanced in the diabetic state, however, they are improved by VOSO4 treatment, and (2) 1O2 is generated during CYP2E1-dependent substrate oxygenation.

Age Factors↗

PubMed2005

Estimation of the age of human bloodstains by electron paramagnetic resonance spectroscopy: long-term controlled experiment on the effects of environmental factors.

In this study, we examined the efficacy and limitations of electron paramagnetic resonance (EPR) for estimating the age of human bloodstains. At 77K, human bloodstains give four striking EPR signals in the g=6.2 (g6), 4.3 (g4), 2.27 (H) and 2.005 (R) regions due to ferric high-spin, ferric non-heme, ferric low-spin and free radical species, respectively. We found that plotting double logarithms of the EPR intensity ratio of H/g4 versus days past bleeding gave a linear correlation up to 432 days with an error range within 25% of the actual number of days under controlled conditions. However, environmental factors such as differences of absorbent, light exposure and fluctuations of storage temperature affected the changes of these EPR-active compounds, which result in misestimation of the time since bleeding occurred. Therefore, one should take such factors into account in estimating the period since bleeding by this method.

Absorption↗

PubMed2005

Synthesis and insulin-mimetic activities of metal complexes with 3-hydroxypyridine-2-carboxylic acid.

Metal complexes of 3-hydroxypyridine-2-carboxylic acid (H(2)hpic), [Co(Hhpic)(2)(H(2)O)(2)] (1), [Fe(Hhpic)(2)(H(2)O)(2)] (2), [Zn(Hhpic)(2)(H(2)O)(2)] (3), [Mn(Hhpic)(2)(H(2)O)(2)] (4), and [Cu(Hhpic)(2)] (5) have been synthesized and characterized by mass spectrometry, elemental analysis, magnetic susceptibility, infrared, electronic absorption and electron paramagnetic resonance (EPR) spectroscopies. The solid-state structure of 1 has been established by X-ray crystallography. The EPR spectra of 4 and 5 displayed six and four-line hyperfine splitting patterns, respectively, due to coupling of the unpaired electron with the (55)Mn (I=5/2) nucleus and the (63)Cu (I=3/2) nucleus. In the EPR spectrum of 5, an additional five-line super-hyperfine splitting pattern was observed at 77 K, caused by additional interaction of the unpaired electron with ligand nitrogen atoms (I=1), indicating that the structure of 5 was retained in dimethyl sulfoxide solution. The insulin-mimetic activity of these complexes was evaluated by means of in vitro measurements of the inhibition of free fatty acid (FFA) release from epinephrine-treated, isolated rat adipocytes. Complex 5 was found to exhibit the most potent insulin-mimetic activity among the complexes examined in this study.

Adipocytes↗

PubMed2005

Detection of reactive oxygen species in the skin of live mice and rats exposed to UVA light: a research review on chemiluminescence and trials for UVA protection.

The harmful effects of ultraviolet (UV) exposure on the skin are associated with the generation of reactive oxygen species (ROS) such as superoxide anion radical ( O(2)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radical ( OH), and singlet oxygen ((1)O(2)) as well as with lipid peroxides and their radicals (LOOH and LOO ). To give direct proof that such ROS are generated in UV-exposed skin, we proposed the in vivo detection and imaging method in which both a sensitive and specific chemiluminescence (CL) probe, such as CLA, and an ultralow-light imaging apparatus with a CCD camera were used. With this method we found that O(2)(-) is formed intrinsically and that (1)O(2) and O(2)(-) are generated in the UVA-exposed skin of mice. In addition, we indicated that antioxidative ability against ROS in the skin of hairless rats decreased as age increased. Using these findings, we demonstrated the protective abilities of sodium ascorbate, caffeic acid, essential aroma oils, and zinc(ii) ion and its complexes, which we administered to mice both topically and orally. We present a review for the current state of our research proposing the sensitive CL method as a useful in vivo tool in photobiological research for the detection of oxidative stress as well as for the evaluation of antioxidative agents to the skin.

Animals↗

PubMed2005

The pharmacology of the insulinomimetic effect of zinc complexes.

In developing new insulinomimetic zinc(II) complexes with different coordination structures and with a blood glucose-lowering effect to treat type 2 diabetic animals, we found a potent bis(maltolato)zinc(ll) complex, Zn(mal)(2). Using the complex as the leading compound, we examined the in vitro and in vivo structure-activity relationships of Zn(mal)(2) and its related complexes in respect to the inhibition of free fatty acids (FFA) release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine (adrenaline), and hypoglycemic activity. Among the compounds tested, a new Zn(II) complex with allixin that was isolated from garlic, bis(allixinato)Zn(II), Zn(alx)(2), was found to exhibit the highest insulin-mimetic and hypoglycemic activities in type 2 KK-A(y) diabetic mice. On the basis of the results, Zn(alx)(2), complex was proposed to be a potent candidate for the treatment of type 2 diabetes.

Animals↗

PubMed2005

A family of insulinomimetic zinc(II) complexes of amino ligands with Zn(Nn) (n=3 and 4) coordination modes.

Several metal ions and their complexes have been known to mimic the action of insulin in in vitro and in vivo systems. We prepared a family of Zn(II) complexes derived from amino ligands with Zn(Nn) (n=3 and 4) coordination modes, the insulinomimetic activity being estimated by an inhibitory effect of free fatty acid release from isolated rat adipocytes treated with epinephrine. In comparison with the positive controls VOSO(4) and ZnSO(4), Zn(II)-amine complexes with stability constants (log beta) lower than 11.5 exhibited higher insulinomimetic activities. Among them, a bis(2-aminomethyl pyridinato)Zn(II) (Zn(2-ampy)(2)(2+)) complex with the highest insulinomimetic activity and a higher stability constant but lower than 11.5 was selected, and subjected to in vivo evaluation in KK-A(y) mice with a genetically type 2 diabetes mellitus. The high blood glucose level of the mice was lowered by daily intraperitoneal injections of Zn(2-ampy)(2)(2+) at a dose of 2 mg Zn/kg body weight for 14 days. Based on the results, Zn(2-ampy)(2)(2+) with Zn(N(4)) coordination mode was proposed to have both a high in vitro insulinomimetic activity and an in vivo blood glucose lowering effect.

Adipocytes↗

PubMed2005

Improvement of diabetic states in streptozotocin-induced type 1 diabetic rats by vanadyl sulfate in enteric-coated capsules.

Chronic oral administration of vanadyl sulfate has recently been shown to improve the state of type 2 diabetic subjects. Mild gastrointestinal symptoms and side effects, however, have been observed in some subjects. To find safer and more effective dosages, we have developed an enteric-coated capsule containing solid vanadyl sulfate (ECC/VS), which enhances the bioavailability of vanadyl sulfate to almost double that of vanadyl sulfate solution. ECC/VS was chronically administered to treat streptozotocin-induced diabetic rats (STZ-rats), an animal model of type 1 diabetes mellitus, and an equivalent blood-glucose-lowering effect was observed at half the doses of vanadyl sulfate alone. In addition, we observed almost the same total vanadium levels in the serum after chronic administration of ECC/VS as those of vanadyl sulfate alone, suggesting that plasma vanadium levels correlate with the hypoglycaemic activity of vanadyl sulfate. These results indicate that oral ECC/VS improves the diabetic state by enhancing the uptake of vanadium in STZ-rats. These findings will be useful in designing clinical trials of vanadyl sulfate for diabetic subjects.

Administration, Oral↗

PubMed2005

Evaluation of distribution patterns for copper and zinc in metallothionein and superoxide dismutase in chronic liver diseases and hepatocellular carcinoma using high-performance liquid chromatography (HPLC).

It has been reported that the copper (Cu) content of hepatocytes increases in chronic liver diseases and small hepatocellular carcinoma (HCC). In cells, Cu exists mainly as Cu-metallothionein (MT) or Cu, zinc (Zn)-superoxide dismutase (SOD). In this study, we investigated the biochemical state of Cu in the hepatocytes of patients with HCC using high-performance liquid chromatography (HPLC). The subjects of present study were 23 patients with HCC who underwent liver resection. The cancerous tissue and non-cancerous hepatic parenchyma with chronic disease were analyzed. In addition, as a normal control, hepatic tissue was collected at autopsy from 13 patients with no liver disease. Each sample was diluted with buffer, chilled, homogenized, and centrifuged. The supernatant was fractionated using HPLC. The metal contents of each fraction were measured using a desktop-type inductively coupled plasma (ICP) emission spectrochemical analyzer. HPLC analysis showed that MT existed mainly as Zn-MT in the normal hepatic tissue. The case of Cu,Zn-MT was significantly greater than Zn-MT in the non-cancerous, but diseased hepatic parenchyma than in the normal hepatic tissue (p<0.01). In comparison with non-cancerous hepatic parenchyma, the Cu-MT in the cancerous section was significantly greater than the Cu,Zn-MT (p<0.01). The Cu content for MT was significantly higher in small HCC (<40 mm) (p<0.01), and the absence of Cu or Zn in the MT fraction was significantly more frequent in the large HCC (>or=40 mm) (p<0.01). The Cu and Zn content for SOD in the samples showed no significant difference. Increase in the Cu content in the cancerous hepatic tissue were, thought to be reflecting changes in the distribution of Cu in the MT fraction of hepatic tissues.

Aged↗

PubMed2005

In vitro alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide.

We found alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide (6mpa-ma) which showed the highest blood glucose lowering effect in Zn(II) complexes with picolinamide derivatives in KK-A(y) mice. The Zn(II) complex showed strong alpha-glucosidase inhibitory activity greater by about eighty times (substrate: maltose) and forty times (substrate: sucrose) compared with acarbose.

Animals↗

PubMed2005

Possible involvement of singlet oxygen species as multiple oxidants in p450 catalytic reactions.

Cytochrome P450 (P450) constitutes a superfamily of enzymes which activate dioxygen and carry out monooxygenation reactions of large numbers of endogenous and xenobiotic compounds. Drug metabolism is a particularly important P450 function, and, therefore, elucidating the metabolic products and pathways of drugs is essential for drug development. To explain the substrate selectivity of P450 reactions, it is necessary to understand the formation of multiple activated oxygen species to determine the type of catalyzed reactions, in addition to conducting structure analyses of P450s. Although an oxo-Fe(IV)-porphyrin-pi-cation radical is regarded as an activated oxygen species in P450 reactions, a nucleophilic Fe(III)-peroxo species has also been proposed as another oxidant. In the past decade, various studies indicated that P450-catalyzed oxygenations are complex, and that a single reaction pathway cannot explain all of the experimental results. In addition, the microsomal P450 system is known to generate reactive oxygen species (ROS). However, the contribution of ROS to P450 reactions remains unclear. We recently found that singlet oxygen (1O2) was involved in both several rat liver microsomal P450 reactions and four human CYP subfamily activities, as confirmed by the ESR spin-trapping method. In this review, we describe the studies that have been conducted on the detection and characterization of ROS in P450 reactions related to drug metabolism that involve the possibility of 1O2 in the P450 catalytic cycle. Gaining an understanding of the activated oxygen species that determine the type of drug metabolism will help us to predict the important metabolites formed.

Catalysis↗

PubMed2005

Essential role of singlet oxygen species in cytochrome P450-dependent substrate oxygenation by rat liver microsomes.

Previously, we reported that singlet oxygen (1O2) was involved in rat liver microsomal P450-dependent substrate oxygenations in such reactions as p-hydroxylation of aniline, O-deethylation of 7-ethoxycoumarin, omega- and (omega-1)-hydroxylations of lauric acid, O-demethylation of p-nitroanisole, and N-demethylation of aminopyrine. In order to confirm the generality of 1O2 involvement, we have further investigated which kinds of reactive oxygen species (ROS) are formed during P450-dependent substrate oxygenation in microsomes. We examined CYP2E1-dependent hydroxylation of p-nitrophenol in rat liver microsomes in the presence of some ROS scavengers, because CYP2E1 has been reported to predominantly generate ROS in the hepatic microsomes and to relate with the oxidative stress in the body. The addition of 1O2 quenchers, beta-carotene, suppressed the hydroxylation of p-nitrophenol. Furthermore, a nonspecific P450 inhibitor, SKF525A, and a ferric chelator, deferoxamine, both suppressed the hydroxylation. No other ROS scavengers such as superoxide dismutase (SOD), catalase, or mannitol altered the reaction. 1O2 was detectable during the reaction in the microsomes as measured by an electron spin resonance (ESR) spin-trapping method when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin-trapping reagent. The 1O2 was quenched by additions of beta-carotene, p-nitrophenol, and SKF525A. The reactivity of p-nitrophenol and 1O2 correlated linearly with its hydroxylation rate in the microsomes. On the basis of these results, we conclude that 1O2 contributes to the p-nitrophenol hydroxylation in rat liver microsomes, by adding a new example of 1O2 involvement in the CYP2E1-dependent substrate oxygenations.

Animals↗

PubMed2005

[Therapeutic potential of vanadium in treating diabetes mellitus].

The patients suffered from diabetes mellitus (DM) are increasing year by year through the world. DM is classified into two groups, insulin-dependent type 1 and non-insulin-dependent type 2. Recent research has demonstrated that vanadate (VO3-, oxidation state+5) and vanadyl (VO2+, oxidation state+4) both mimic various actions of insulin in cellular systems. In 1985, vanadate given orally as a drinking water to streptozotocin-induced hyperglycemic type 1 diabetic rats (STZ-rats) was found to reduce the high levels of blood glucose down to normal levels and ameliorated many of the aberrations induced by hyperglycemia. In 1990, we proposed first orally active vanadyl complexes such as vanadyl-cysteine methylester and vanadyl-oxalate complexes in STZ-rats. Since then, we have developed orally active vanadyl complexes with different coordination modes. Among them, vanadyl-picolinate complexes with VO(N2O2) coordination mode were found to be potent orally active insulin-mimetic agents, on the basis of the results on in vitro test using isolated rat adipocytes with respect to the inhibition of the release of free fatty acids (FFA) from the cells and in vivo evaluation (intraperitoneal injection and oral administration) in STZ-rats. Based on the results, the usefulness of vanadium complexes in treating and preventing DM has been revealed, proposing a possible action mechanism.

Adipocytes↗

PubMed2004

A new insulin-mimetic bis(allixinato)zinc(II) complex: structure-activity relationship of zinc(II) complexes.

During the investigation of the development of insulin-mimetic zinc(II) complexes with a blood glucose-lowering effect in experimental diabetic animals, we found a potent bis(maltolato)zinc(II) complex, Zn(ma)(2), exhibiting significant insulin-mimetic effects in a type 2 diabetic animal model. By using this Zn(ma)(2) as the leading compound, we examined the in vitro and in vivo structure-activity relationships of Zn(ma)(2) and its related complexes. The in vitro insulin-mimetic activity of these complexes was determined by the inhibition of free fatty acid release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine. A new Zn(II) complex with allixin isolated from garlic, Zn(alx)(2), exhibited the highest insulin-mimetic activity among the complexes analyzed. The insulin-mimetic activity of the Zn(II) complexes examined strongly correlated (correlation coefficient=0.96) with the partition coefficient (log P) of the ligand, indicating that the activity of Zn(ma)(2)-related complexes depends on the lipophilicity of the ligand. The blood glucose-lowering effects of Zn(alx)(2) and Zn(ma)(2) were then compared, and both complexes were found to normalize hyperglycemia in KK- A(y) mice after a 14-day course of daily intraperitoneal injections. However, Zn(alx)(2) improved glucose tolerance in KK- A(y) mice much more than did Zn(ma)(2), indicating that Zn(alx)(2) possesses greater in vivo anti-diabetic activity than Zn(ma)(2). In addition, Zn(alx)(2) improved leptin resistance and suppressed the progress of obesity in type 2 diabetic KK- A(y) mice. On the basis of these observations, we conclude that the Zn(alx)(2) complex is a novel potent candidate for the treatment of type 2 diabetes mellitus.

Adipocytes↗

PubMed2004

Implication of the differential roles of metallothionein 1 and 2 isoforms in the liver of rats as determined by polyacrylamide-coated capillary zone electrophoresis.

Metallothioneins (MTs), determined by polyacrylamide-coated capillary zone electrophoresis (CZE), coincided well with those described by enzyme-linked immunosorbent assay. By using CZE, MT isoforms 1 (MT-1) and 2 (MT-2) were well separated and determined in the liver cytosol of LEC rats and Wistar rats administered CdCl(2). The total concentrations of MTs in the liver cytosol of LEC rats increased age-dependently as 1.0, 2.1, and 7.2mg/g wet weight of the liver at the age of 5, 10, and 15 weeks, respectively, and those of Wistar rats that had received daily CdCl(2) also increased with time of CdCl(2) as 0.5 and 1.2mg/g wet weight of the liver for 3 and 6 consecutive administration days, respectively. The MT-1/MT-2 ratio in the liver cytosol of LEC rats decreased age-dependently as 1.75, 1.49, and 0.76 at the age of 5, 10, and 15 weeks, respectively. In contrast, that of Wistar rats increased with time of exposure to the metal ion CdCl(2) as 1.1 and 1.6 for 3 and 6 administration days, respectively. Copper accumulation in the liver of LEC rats has already been reported. The present results indicated that the mechanism of the induction of MT synthesis differs between LEC rats, who lack ATP7B, and Wistar rats, who were given a toxic metal ion. On the basis of these results, we propose that MT-1 is related to the metabolism or detoxification of toxic metals such as Cd, and in contrast, MT-2 is responsible for the homeostasis of essential metals such as Cu.

Acrylic Resins↗

PubMed2004

The action mechanism of zinc(II) complexes with insulinomimetic activity in rat adipocytes.

Zinc (Zn), an essential trace element, and its complexes have recently been known to exhibit insulinomimetic activities. However, the action mechanism of Zn(II) has yet been obscure. The purpose of the present study was to estimate the action mechanism of the Zn(II) complexes. We found first that Zn given in the chemical forms such as Zn(maltolate)2 and Zn(threoninate)2 complexes is highly uptaken in the isolated rat adipocytes compared with that of Zn(picolinate)2. Then, the action mechanism for the insulinomimetic activities was examined in terms of free fatty acid release from the adipocytes. Four Zn(II) compounds, ZnSO4, Zn(picolinate)2, Zn(maltolate)2, and Zn(threoninate)2, inhibited the free fatty acid release from the adipocytes treated with epinephrine (adrenaline). By using several inhibitors for fatty acids and glucose metabolisms in the adipocytes, the following results were obtained. (1) Zn(picolinic acid)2 complex acts on the insulin receptor and PI3-k, which relate to the glucose uptake, as indicated by the experiments using hydroxy-2-naphthalenylmethyl phosphonic acid tris acetoxy methyl ester (HNMPA-(AM)3) and wortmannin, respectively. (2) ZnSO4, and Zn(maltolate)2 and Zn(threoninate)2 complexes affect a glucose transporter 4 (GLUT 4), which is involved in the glucose uptake as indicated by the results using cytochalasin B. (3) Four Zn(II) compounds affect the activation of the phosphodiesterase as indicated by the experiments using cilostamide. These results indicate that the Zn(II) compounds promote the glucose uptake into the adipocytes by affecting at least three sites in the adipocytes, which in turn normalize the blood glucose levels in the experimental diabetic animals.

Adipocytes↗

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

Synthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid.

Two chargeless VO(IV) complexes with 3-hydroxypyridine-2-carboxylic acid (H2hpic), [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)].3H2O (1) and the cyclic tetramer [(VO)4(mu-(hpic-O,O',N))4(H2O)4].8H3O (2), have been synthesized and characterized by elemental analysis, mass, infrared, electronic absorption, electron spin resonance (ESR) spectroscopies, and X-ray crystallography. Their coordination structures are similar to each other (and 1 is readily transformed into 2), but are quite different from that of bis(pyridine-2-carboxylato)oxovanadium(IV). The magnetic susceptibility of 2 indicates the presence of a weak ferromagnetic intramolecular interaction between the V atoms at low temperature, in addition to a weak antiferromagnetic intermolecular interaction. The ESR signal of 2 was broad, while 1 showed an eight-line hyperfine splitting pattern due to coupling of the unpaired electron with the 51V nucleus (I=7/2). The ESR spectrum and cyclic voltammogram of 2 clearly show that the cyclic tetramer remains intact in solution. The insulinomimetic activity of 1 and 2 was evaluated by means of in vitro measurements of the inhibition of free fatty acid release from epinephrine-treated isolated rat adipocytes. While 1 exerted higher insulinomimetic activity than VOSO4, the activity of 2 was significantly lower than that of VOSO4. Hence 2 appears to retain its cyclic structure during the in vitro test. These results indicate that the rational ligand design for VO complexes might be a promising approach to obtain superior insulinomimetic activity.

Adipocytes↗