Mechanism on Insulin-Like Action of Vanadyl Sulfate: Studies on Interaction between Rat Adipocytes and Vanadium Compounds.

Nakai, Masami; Watanabe, Hiromi; Fujiwara, Chikako; Kakegawa, Hisao; Satoh, Toshio; Takada, Jitsuya; Matsushita, Rokuji

doi:10.1248/bpb.18.719

Cited by 148 publications

(118 citation statements)

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“…This supports the idea that administrated vanadyl ions are bound to proteins in vivo [9,[22][23][24]. The ESEEM results also suggest that, in the vanadyl-protein (or -peptide) complex, the vanadyl ion is coordinated by the e-amine of Lys or the Nterminal o-amine.…”

Section: Implications For the Coordinating Nitrogen In The Organssupporting

confidence: 81%

Detection of vanadyl‐nitrogen interaction in organs of the vanadyl‐treated rat: electron spin echo envelope modulation study

et al. 1995

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Section: Implications For the Coordinating Nitrogen In The Organssupporting

confidence: 81%

Detection of vanadyl‐nitrogen interaction in organs of the vanadyl‐treated rat: electron spin echo envelope modulation study

et al. 1995

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“…From this result, the incubation period was fixed at 3 h, similarly to the FFA-release assay. 35) During the 3-h incubation period, insulin induced a concentration-dependent increase in the glucose-uptake at 0-2.2 nM (0-300 mU/ml) (Fig. 1B).…”

Section: Resultsmentioning

confidence: 87%

“…Glucose-Uptake Enhancement and FFA-Release Inhibition by Insulin and VOSO 4 in Isolated Rat Adipocytes Treated with Epinephrine Because FFA-release from adipocytes was significantly stimulated by epinephrine, 28,29,35) the correlation between the inhibitory activity of FFA-release and the glucose-uptake ability of vanadyl compounds was examined in the presence of 10 mM epinephrine.…”

Section: Resultsmentioning

confidence: 99%

“…5,6,27) In 1995, we proposed a new in vitro assay, based on the inhibition of FFA (free fatty acids)-release from isolated rat adipocytes treated with epinephrine (adrenalin), which is simple and convenient compared with the use of RI reagents. 35) By this in vitro assay, we have evaluated some insulin-mimetic activities of vanadyl complexes with different chemical structures and coordination modes such as VO(O 4 ), 36) VO(N 2 O 2 ), [37][38][39][40][41][42][43] VO(S 2 N 2 ), 36) VO(S 2 O 2 ), 44,45) VO(N 3 O), 39) and VO(N 4 ). 28) Our results indicate that the complexes with a strong ability to inhibit FFA-release from adipocytes lowered the high blood glucose levels in type 1 and 2 diabetic animals more effectively than VOSO 4 .…”

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confidence: 99%

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Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

Adachi

Sakurai

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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We have recently proposed the existence of some potent vanadyl complexes with blood glucose-lowering activity in experimental diabetic animals based on the results of an in vitro FFA (free fatty acids)-release assay in isolated rat adipocytes treated with epinephrine and evidence of an in vivo blood glucose lowering effect in experimental diabetic animals. However, the FFA assay depends indirectly on the glucose-uptake of vanadyl complexes in adipocytes. It is therefore necessary to develop a more reliable in vitro glucose-uptake assay, in place of the glucose uptake method using radioactive compounds such as 14 C-glucose, to identify insulin-mimetic vanadyl complexes. In the present study, we proposed a combined in vitro assay by using the conventional glucose oxidase method for glucose-uptake and FFA assay in isolated rat adipocytes. Insulin, vanadyl sulfate (VOSO 4 ), bis(picolinato)vanadyl (VO(pa) 2 ), and bis(6-methylpicolinato)vanadyl (VO(6mpa) 2 ) complexes exhibited concentration-dependent uptake of (؉)-D-glucose and inhibition of FFA release in the adipocytes treated with epinephrine. Vanadyl complexes were found to accelerate glucose-uptake at lower concentrations than VOSO 4 . In vitro high insulin-mimetic activity of VO(pa) 2 and VO(6mpa) 2 were thus indicated by both glucose-uptake and FFA-release, with the insulin-mimetic activity of VO(6mpa) 2 being higher than that of VO(pa) 2 , as suggested by the partition coefficient (0.330 for VO(pa) 2 and 0.595 for VO(6mpa) 2 ). The proposed assay provides a more reliable method than each single method for the evaluation of in vitro insulin-mimetic activity of compounds.Key words vanadyl compound; glucose-uptake assay; free fatty acids (FFA)-release assay; insulin-mimetic effect; adipocyte 428

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“…1D), suggesting that an interference with glucose metabolism had occurred by unknown mechanisms that require further studies in order to be clarified. We may just speculate that if in the b cells of hyperlipacidemic Dex-treated rats, triglyceride synthesis and subsequent lipolysis are implicated in the generation of lipid signaling molecules enhancing glucosestimulated insulin secretion, then the concomitant exposure to vanadium, which has been reported to exert an antilipolytic action (42), could interfere with this mechanism. Such a hypothesis is in line with the fact that, in our Dex plus VOSO 4 -treated rats, a subsequent glucose stimulation in the presence of a cAMP agonist, which might also activate b-cell triacylglycerol lipase (43), resulted in a significantly greater insulin release than in age-matched controls (not shown).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone-induced insulin resistance and pancreatic adaptive response in aging rats are not modified by oral vanadyl sulfate treatment

Fierabracci

Novelli

Bombara

et al. 2001

European Journal of Endocrinology

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Objective: To explore the adaptive response of the endocrine pancreas in vivo and in vitro and the possible beneficial effect of the insulino-mimetic agent vanadyl sulfate (VOSO 4 ), using glucocorticoid treatment to increase insulin resistance, in aging rats. Design and Methods: Dexamethasone (Dex) (0.13 mg/kg b.w.) was administered daily for 13 days to 3-and 18-month old Sprague-Dawley rats and oral VOSO 4 was given from the 5th day. Plasma glucose, insulin and free fatty acids (FFA) concentrations were measured during these treatments and the insulin secretory response of the isolated perfused pancreas was assessed at the end of the experiment. Results and Conclusions: In both young and aging rats, particularly in the latter, hyperinsulinemia and increased in vitro insulin responsiveness to glucose were observed in response to Dex treatment, concomitant with an increase in plasma FFA concentrations. Thus, in glucocorticoid-treated animals, the b-cell adaptive response occurred in both age groups and could possibly be mediated by increased circulating FFA; however, it was insufficient to prevent hyperglycemia in 60% of aging animals. Oral VOSO 4 administration failed to correct Dex-induced alterations in glucose and lipid metabolism, although it influenced in vitro b-cell responsiveness to stimuli in aging rats.

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Mechanism on Insulin-Like Action of Vanadyl Sulfate: Studies on Interaction between Rat Adipocytes and Vanadium Compounds.

Cited by 148 publications

References 0 publications

Detection of vanadyl‐nitrogen interaction in organs of the vanadyl‐treated rat: electron spin echo envelope modulation study

Detection of vanadyl‐nitrogen interaction in organs of the vanadyl‐treated rat: electron spin echo envelope modulation study

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

Dexamethasone-induced insulin resistance and pancreatic adaptive response in aging rats are not modified by oral vanadyl sulfate treatment

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