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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Perspectives in Diabetes|
June 01 1993
Hyperglycemic Pseudohypoxia and Diabetic Complications
Joseph R Williamson;
Joseph R Williamson
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Katherine Chang;
Katherine Chang
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Myrto Frangos;
Myrto Frangos
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Khalid S Hasan;
Khalid S Hasan
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Yasuo Ido;
Yasuo Ido
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Takahiko Kawamura;
Takahiko Kawamura
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Jens R Nyengaard;
Jens R Nyengaard
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Maria van Den Enden;
Maria van Den Enden
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Charles Kilo;
Charles Kilo
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Ronald G Tilton
Ronald G Tilton
Departments of Pathology, Pediatrics, and Internal Medicine, Washington University School of Medicine
St. Louis, Missouri
Department of Internal Medicine, Chubu Rosai Hospital
Nagoya, Japan
Stereological Research Lab, Aarhus University
Aarhus, Denmark
Department of Internal Medicine, Middelheim Hospital
Antwerp, Belgium
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Address correspondence and reprint requests to Dr. Joseph R. Williamson, Department of Pathology, Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110.
Diabetes 1993;42(6):801–813
Article history
Received:
February 02 1993
Revision Received:
March 12 1993
Accepted:
March 12 1993
PubMed:
8495803
Citation
Joseph R Williamson, Katherine Chang, Myrto Frangos, Khalid S Hasan, Yasuo Ido, Takahiko Kawamura, Jens R Nyengaard, Maria van Den Enden, Charles Kilo, Ronald G Tilton; Hyperglycemic Pseudohypoxia and Diabetic Complications. Diabetes 1 June 1993; 42 (6): 801–813. https://doi.org/10.2337/diab.42.6.801
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