Stress and Vascular Responses: Oxidative Stress and Endothelial Dysfunction in the Insulin-Resistant State

Shinozaki, Kazuya; Kashiwagi, Atsunori; Morimoto, Masahiro; Okamura, Tomio

doi:10.1254/jphs.91.187

Cited by 27 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At a high level, BH 2 may bind to NOS in the place of BH 4 , resulting in the production of active oxygens (6, 42 -45) which are potentially detrimental to tissues. Actually, the possible relationships between an elevated BH 2 level and various circulatory disorders have been suggested in high fructose-induced diabetes model rats (46,47). In the present study, administration of 6RBH 4 was demonstrated to evoke a BH 2 surge and that use of MTX results in a long lasting rise in BH 2 levels in blood.…”

Section: Discussionsupporting

confidence: 55%

Tetrahydrobiopterin Uptake in Supplemental Administration: Elevation of Tissue Tetrahydrobiopterin in Mice Following Uptake of the Exogenously Oxidized Product 7,8-Dihydrobiopterin and Subsequent Reduction by an Anti-folate-Sensitive Process

2004

View full text Add to dashboard Cite

Abstract. In order to increase the tissue level of tetrahydrobiopterin (BH 4 ), supplementation with 6R-tetrahydrobiopterin (6RBH 4 ) has been widely employed. In this work, the effectiveness of 6RBH 4 was compared with 7,8-dihydrobiopterin (7,8BH 2 ) and sepiapterin by administration to mice. Administration of 6RBH 4 was the least effective in elevating tissue BH 4 levels in mice while sepiapterin was the best. In all three cases, a dihydrobiopterin surge appeared in the blood. The appearance of the dihydrobiopterin surge after BH 4 treatment suggested that systemic oxidation of the administered BH 4 had occurred before accumulation of BH 4 in the tissues. This idea was supported by the following evidences: 1) An increase in tissue BH 4 was effectively inhibited by methotrexate, an inhibitor of dihydrofolate reductase which reduces 7,8BH 2 to BH 4 . 2) When the unnatural diastereomer 6SBH 4 was administered to mice, a large proportion of the recovered BH 4 was in the form of the 6R-diastereomer, suggesting that this BH 4 was the product of a dihydrofolate reductase process by which 7,8BH 2 converts to 6RBH 4 . These results indicated that the exogenous BH 4 was oxidized and the resultant 7,8BH 2 circulated through the tissues, and then it was incorporated by various other tissues and organs through a pathway shared by the exogenous sepiapterin and 7,8BH 2 in their uptake. It was demonstrated that maintaining endogenous tetrahydrobiopterin in tissues under ordinary conditions was also largely dependent on an methotrexate-sensitive process, suggesting that cellular tetrahydrobiopterin was maintained both by de novo synthesis and by salvage of extracellular dihydrobiopterin.

show abstract

Section: Discussionsupporting

confidence: 55%

Tetrahydrobiopterin Uptake in Supplemental Administration: Elevation of Tissue Tetrahydrobiopterin in Mice Following Uptake of the Exogenously Oxidized Product 7,8-Dihydrobiopterin and Subsequent Reduction by an Anti-folate-Sensitive Process

2004

View full text Add to dashboard Cite

show abstract

“…We do not understand the influence insulin resistance and hyperinsulinemia has on superoxide formation. Under insulin-resistant conditions, levels of tetrahydrobiopterin are reduced, and the production of superoxide by nitric oxide synthases is increased (36). In our studies, serum levels of insulin were increased at 28 wk of age, but, after 36 -40 wk of age, serum insulin levels were decreased to near control values.…”

Section: Discussioncontrasting

confidence: 44%

Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats

Oltman¹,

Coppey²,

Gellett³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

115

130

View full text Add to dashboard Cite

We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12-14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8-10 wk of age in ZDF diabetic rats and after approximately 16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia.

show abstract

“…[8][9][10][11] It has been demonstrated that a statin therapy can improve atherosclerosis without any exacerbation of diabetes mellitus. 2,12) A statin therapy is now getting to be strongly recommended for diabetic patients with hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 99%

HMG-CoA Reductase Inhibitors Do Not Improve Glucose Intolerance in Spontaneously Diabetic Goto-Kakizaki Rats

Satoh

Keimatsu

Kanda

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

We examined whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve glucose intolerance in spontaneously diabetic Goto-Kakizaki (GK) rats or not. The fasting blood glucose, plasma insulin, and serum cholesterol levels were significantly higher in GK rats than those in age-matched Wistar rats. All rats were given orally once a day 0.5% carboxymethylcellulose, pravastatin 8 mg/kg, simvastatin 8 mg/kg, or atorvastatin 8 mg/kg. An oral glucose tolerance test (OGTT) was performed before and 3, 6 and 12 weeks after statin treatments. The hyperglycemic response to OGTT in GK rats significantly exceeded that in Wistar rats. The plasma insulin level in GK rats increased with age until 14-week-old (treated for 6 weeks), and then decreased. Glucose intake significantly increased the plasma insulin in almost all rats. The increment of plasma insulin due to OGTT in GK rats appeared to be less than that in Wistar rats, because the basal level was already high in GK rats. Pravastatin, simvastatin, and atorvastatin did not modify changes in blood glucose and plasma insulin induced by glucose intake. In conclusion, long-term treatments of GK rats with statins did not improve glucose intolerance observed during OGTT.

show abstract

Stress and Vascular Responses: Oxidative Stress and Endothelial Dysfunction in the Insulin-Resistant State

Cited by 27 publications

References 34 publications

Tetrahydrobiopterin Uptake in Supplemental Administration: Elevation of Tissue Tetrahydrobiopterin in Mice Following Uptake of the Exogenously Oxidized Product 7,8-Dihydrobiopterin and Subsequent Reduction by an Anti-folate-Sensitive Process

Tetrahydrobiopterin Uptake in Supplemental Administration: Elevation of Tissue Tetrahydrobiopterin in Mice Following Uptake of the Exogenously Oxidized Product 7,8-Dihydrobiopterin and Subsequent Reduction by an Anti-folate-Sensitive Process

Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats

HMG-CoA Reductase Inhibitors Do Not Improve Glucose Intolerance in Spontaneously Diabetic Goto-Kakizaki Rats

Contact Info

Product

Resources

About