Amelioration of insulin resistance in diabetic ob/ob mice by a new type of orally active insulin–mimetic vanadyl complex: Bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) with VO(S2O2) coordination mode

Takeshita, S; Kawamura, Ikuo; Yasuno, Tohru; Kimura, C.; Yamamoto, Tadashi; Seki, Jiro; Tamura, Atsutaka; Sakurai, Hiromu; Goto, Toshio

doi:10.1016/s0162-0134(01)00192-1

Cited by 54 publications

(36 citation statements)

References 41 publications

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“…27 In the present series of experiments, none of the rats died in any of the studies conducted, and no gastrointestinal, hepatic, or renal toxicity was observed after 14 days of VO(OPT) treatment, as reported previously. 27,28 Moreover, VO(OPT)-treated rats continue to gain weight throughout the experimental period, as reported previously. 27,28,33 This suggests that the reduced weight gain caused by VO(OPT) administration is attributable to the reduced food and fluid intake.…”

Section: Bhuiyan Et Al Vo(opt) Augments Myocardial Hypertrophysupporting

confidence: 84%

“…27,28 Moreover, VO(OPT)-treated rats continue to gain weight throughout the experimental period, as reported previously. 27,28,33 This suggests that the reduced weight gain caused by VO(OPT) administration is attributable to the reduced food and fluid intake. 27,28,33 In conclusion, the most important observation presented here is that simultaneous severe reduction of eNOS and Akt activity in OVX-PO female rats likely triggers compensatory hypertrophy with increased heart contractility ( Figure S6).…”

Section: Bhuiyan Et Al Vo(opt) Augments Myocardial Hypertrophysupporting

confidence: 77%

“…27,28,33 This suggests that the reduced weight gain caused by VO(OPT) administration is attributable to the reduced food and fluid intake. 27,28,33 In conclusion, the most important observation presented here is that simultaneous severe reduction of eNOS and Akt activity in OVX-PO female rats likely triggers compensatory hypertrophy with increased heart contractility ( Figure S6). Potentiation of the Akt and eNOS signaling pathways, along with inhibition of dystrophin breakdown, by treatment with VO(OPT) after OVX-PO likely contributes to increased survival after acute cardiac stress caused by chronic ␤-adrenergic stimulation ( Figure S6).…”

Section: Bhuiyan Et Al Vo(opt) Augments Myocardial Hypertrophymentioning

confidence: 99%

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Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

et al. 2009

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Abstract-We here investigated the effect of bis(1-oxy-2-pyridinethiolato) oxovanadium (IV), [VO(OPT)], against myocardial hypertrophy and cardiac functional recovery in pressure overload-induced hypertrophy in ovariectomized female rats and defined mechanisms underlying its cardioprotective action. Wistar rats subjected to bilateral ovariectomy were further treated with abdominal aortic stenosis. VO(OPT) (containing 1.25 and 2.50 mg of vanadium per kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. Treatment with VO(OPT) significantly inhibited pressure overload-induced increase both in the heart weight:body weight ratio and the lung weight:body weight ratio. VO(OPT) also attenuated hypertrophy-induced impaired left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contractility (Ϯdp/dt max ). VO(OPT) treatment significantly restored pressure overload-induced impaired endothelial NO synthase activity with concomitant increased phosphorylation of endothelial NO synthase (Ser1179). Moreover, VO(OPT) treatment significantly restored pressure overload-induced reduced Akt activity, as indicated by increased phosphorylation at Ser473 and at Thr308. Treatment with VO(OPT) also secondarily inhibited calpastatin and dystrophin breakdown and decreased myosin light chain phosphorylation. Finally, VO(OPT) treatment significantly attenuated mortality after repeated isoproterenol administration in pressure overloaded-ovariectomized rats. Taken together, VO(OPT) attenuates cardiac myocytes hypertrophy in vivo in pressure overload-induced hypertrophy in ovariectomized rats and prevents the process from hypertrophy to heart failure. These effects are mediated by inhibition of calpastatin and dystrophin breakdown in addition to increased Akt and endothelial NO synthase activities. Key Words: myocardial hypertrophy Ⅲ protein kinase B (Akt) Ⅲ endothelial nitric oxide synthase (eNOS) Ⅲ ovariectomy Ⅲ dystrophin L eft ventricular (LV) hypertrophy is an independent risk factor for the development of heart failure. 1 Although LV hypertrophy is an adaptive response to pressure and volume overload, this process becomes maladaptive without drug therapy. The pathological cardiac hypertrophy, in turn, triggers the development of heart failure. 2 The search for novel drug treatment has directed attention to cardiac hypertrophy as cardioprotection. 2 Signaling through the phosphatidylinositol 3-kinase/Akt pathway is important for the physiological growth and inhibition of pathological hypertrophy. 3-5 Moreover, physiological hypertrophy induced by exercise training also requires the activation of myocardial Akt. By contrast, pathological hypertrophies induced by pressure overload cause an inactivation of the Akt signal pathway. 6 We have also reported that pressure overload (PO)-induced hypertrophy in ovariectomized (OVX) female rats markedly reduces both endothelial NO synthase (eNOS) protein expression and its activity with concomitantly marked reduced Ak...

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Section: Bhuiyan Et Al Vo(opt) Augments Myocardial Hypertrophysupporting

confidence: 84%

Section: Bhuiyan Et Al Vo(opt) Augments Myocardial Hypertrophysupporting

confidence: 77%

Section: Bhuiyan Et Al Vo(opt) Augments Myocardial Hypertrophymentioning

confidence: 99%

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Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

et al. 2009

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“…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 .…”

mentioning

confidence: 99%

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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“…Infertility is a current feature in obese mouse, this being supported by fatty degeneration of the ovaries, follicular atresia, damaged mitochondria and apoptosis of the ovocytes [82]. Many studies have been run in ob/ob mice such as amelioration of insulin resistance [83], hypoglycemic effects of some polysaccharids [84,85] and complication of NIDDM as diabetic cardiomiopathy [86] and peripheral neuropathy [87].…”

Section: Animal Models Of Non-insulin Dependent Diabetes Mellitus (Nimentioning

confidence: 99%

Development of Improved Animal Models for the Study of Diabetes

Ciobotaru¹

2013

Diabetes Mellitus - Insights and Perspectives

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Amelioration of insulin resistance in diabetic ob/ob mice by a new type of orally active insulin–mimetic vanadyl complex: Bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) with VO(S2O2) coordination mode

Cited by 54 publications

References 41 publications

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

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

Development of Improved Animal Models for the Study of Diabetes

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