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Diabetes, Vol 42, Issue 6 801-813, Copyright © 1993 by American Diabetes Association

ARTICLES

Hyperglycemic pseudohypoxia and diabetic complications

JR Williamson, K Chang, M Frangos, KS Hasan, Y Ido, T Kawamura, JR Nyengaard, M van den Enden, C Kilo and RG Tilton
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.

Vasodilation and increased blood flow are characteristic early vascular responses to acute hyperglycemia and tissue hypoxia. In hypoxic tissues these vascular changes are linked to metabolic imbalances associated with impaired oxidation of NADH to NAD+ and the resulting increased ratio of NADH/NAD+. In hyperglycemic tissues these vascular changes also are linked to an increased ratio of NADH/NAD+, in this case because of an increased rate of reduction of NAD+ to NADH. Several lines of evidence support the likelihood that the increased cytosolic ratio of free NADH/NAD+ caused by hyperglycemia, referred to as pseudohypoxia because tissue partial pressure oxygen is normal, is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural function and plays an important role in the pathogenesis of diabetic complications. These effects of hypoxia and hyperglycemia-induced pseudohypoxia on vascular and neural function are mediated by a branching cascade of imbalances in lipid metabolism, increased production of superoxide anion, and possibly increased nitric oxide formation.
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

Home page
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M. J. Sheetz and G. L. King
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[Abstract] [Full Text] [PDF]

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Protection of ischemic myocardium in diabetics by inhibition of electroneutral Na+-K+-2Cl{-} cotransporter
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[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
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Hyperglycemia Acutely Increases Monocyte Extracellular Signal-Regulated Kinase Activity in Vivo in Humans
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1301 - 1305.
[Abstract] [Full Text]

Home page
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Antiatherogenic Mitochondrial Genotype in Patients With Type 2 Diabetes
Diabetes Care, March 1, 2001; 24(3): 500 - 503.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
J. Calles-Escandon and M. Cipolla
Diabetes and Endothelial Dysfunction: A Clinical Perspective
Endocr. Rev., February 1, 2001; 22(1): 36 - 52.
[Abstract] [Full Text]

Home page
 IOVSHome page
S. Majka, P. McGuire, S. Colombo, and A. Das
The Balance between Proteinases and Inhibitors in a Murine Model of Proliferative Retinopathy
Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 210 - 215.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Kimura, M. Oike, T. Koyama, and Y. Ito
Impairment of endothelial nitric oxide production by acute glucose overload
Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E171 - E178.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
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[Abstract] [Full Text]

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Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1139 - E1144.
[Abstract] [Full Text] [PDF]

Home page
 Vasc MedHome page
M. Meier and G. L King
Protein kinase C activation and its pharmacological inhibition in vascular disease
Vascular Medicine, August 1, 2000; 5(3): 173 - 185.
[Abstract] [PDF]

Home page
 FASEB J.Home page
I. G. OBROSOVA, C. VAN HUYSEN, L. FATHALLAH, X. CAO, M. J. STEVENS, and D. A. GREENE
Evaluation of {alpha}1-adrenoceptor antagonist on diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense
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J. Am. Coll. Cardiol., July 1, 2000; 36(1): 94 - 102.
[Abstract] [Full Text] [PDF]

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