Aarhus University Seal / Aarhus Universitets segl

Jens Randel Nyengaard

Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation. / Ido, Yasuo; Nyengaard, Jens R.; Chang, Kathy; Tilton, Ronald G.; Kilo, Charles; Mylari, Banavara L.; Oates, Peter J.; Williamson, Joseph R.

In: Antioxidants and Redox Signaling, Vol. 12, No. 1, 01.01.2010, p. 39-51.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Ido, Y, Nyengaard, JR, Chang, K, Tilton, RG, Kilo, C, Mylari, BL, Oates, PJ & Williamson, JR 2010, 'Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation', Antioxidants and Redox Signaling, vol. 12, no. 1, pp. 39-51. https://doi.org/10.1089/ars.2009.2502

APA

Ido, Y., Nyengaard, J. R., Chang, K., Tilton, R. G., Kilo, C., Mylari, B. L., Oates, P. J., & Williamson, J. R. (2010). Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation. Antioxidants and Redox Signaling, 12(1), 39-51. https://doi.org/10.1089/ars.2009.2502

CBE

Ido Y, Nyengaard JR, Chang K, Tilton RG, Kilo C, Mylari BL, Oates PJ, Williamson JR. 2010. Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation. Antioxidants and Redox Signaling. 12(1):39-51. https://doi.org/10.1089/ars.2009.2502

MLA

Vancouver

Ido Y, Nyengaard JR, Chang K, Tilton RG, Kilo C, Mylari BL et al. Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation. Antioxidants and Redox Signaling. 2010 Jan 1;12(1):39-51. https://doi.org/10.1089/ars.2009.2502

Author

Ido, Yasuo ; Nyengaard, Jens R. ; Chang, Kathy ; Tilton, Ronald G. ; Kilo, Charles ; Mylari, Banavara L. ; Oates, Peter J. ; Williamson, Joseph R. / Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation. In: Antioxidants and Redox Signaling. 2010 ; Vol. 12, No. 1. pp. 39-51.

Bibtex

@article{742c995b5a23409e8607f22f247ae2cd,
title = "Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation",
abstract = "These experiments were undertaken to assess the importance of cytoplasmic (c) sorbitol oxidation versus mitochondrial (m) pyruvate oxidation in mediating neural and vascular dysfunction attributable to hyperglycemia in diabetic rats. Increased oxidation of sorbitol is coupled to enzymatic reduction of free oxidized NAD +c to reduced NADHc, manifested by an increased ratio of NADH to NAD +c. Likewise, increased oxidation of pyruvate is coupled to reduction of NAD +m to NADHm, which increases the NADH/NAD +m ratio. Specific inhibitors of sorbitol production or sorbitol oxidation normalized: increased diabetic nerve NADH/NAD +c, impaired nerve-conduction velocity, and vascular dysfunction in sciatic nerve, retina, and aorta; however, they had little or no impact on increased NADH/NAD +m. These observations provide, for the first time, strong in vivo evidence for the primacy of sorbitol oxidation versus. pyruvate oxidation in mediating the metabolic imbalances, impaired nerve conduction, and vascular dysfunction evoked by diabetes. These findings are consistent with (a) the fact that oxidation of sorbitol produces {"}prooxidant{"} NADHc uncoupled from subsequent production of {"}antioxidant{"} pyruvate required for reoxidation of NADHc to NAD +c by lactate dehydrogenase, and (b) the hypothesis that neural and vascular dysfunction in early diabetes are caused primarily by increased NADHc, which fuels superoxide production by NADH-driven oxidases. Antioxid. Redox Signal.",
author = "Yasuo Ido and Nyengaard, {Jens R.} and Kathy Chang and Tilton, {Ronald G.} and Charles Kilo and Mylari, {Banavara L.} and Oates, {Peter J.} and Williamson, {Joseph R.}",
year = "2010",
month = jan,
day = "1",
doi = "10.1089/ars.2009.2502",
language = "English",
volume = "12",
pages = "39--51",
journal = "Antioxidants & Redox Signaling",
issn = "1523-0864",
publisher = "Mary AnnLiebert, Inc. Publishers",
number = "1",

}

RIS

TY - JOUR

T1 - Early neural and vascular dysfunctions in diabetic rats are largely sequelae of increased sorbitol oxidation

AU - Ido, Yasuo

AU - Nyengaard, Jens R.

AU - Chang, Kathy

AU - Tilton, Ronald G.

AU - Kilo, Charles

AU - Mylari, Banavara L.

AU - Oates, Peter J.

AU - Williamson, Joseph R.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - These experiments were undertaken to assess the importance of cytoplasmic (c) sorbitol oxidation versus mitochondrial (m) pyruvate oxidation in mediating neural and vascular dysfunction attributable to hyperglycemia in diabetic rats. Increased oxidation of sorbitol is coupled to enzymatic reduction of free oxidized NAD +c to reduced NADHc, manifested by an increased ratio of NADH to NAD +c. Likewise, increased oxidation of pyruvate is coupled to reduction of NAD +m to NADHm, which increases the NADH/NAD +m ratio. Specific inhibitors of sorbitol production or sorbitol oxidation normalized: increased diabetic nerve NADH/NAD +c, impaired nerve-conduction velocity, and vascular dysfunction in sciatic nerve, retina, and aorta; however, they had little or no impact on increased NADH/NAD +m. These observations provide, for the first time, strong in vivo evidence for the primacy of sorbitol oxidation versus. pyruvate oxidation in mediating the metabolic imbalances, impaired nerve conduction, and vascular dysfunction evoked by diabetes. These findings are consistent with (a) the fact that oxidation of sorbitol produces "prooxidant" NADHc uncoupled from subsequent production of "antioxidant" pyruvate required for reoxidation of NADHc to NAD +c by lactate dehydrogenase, and (b) the hypothesis that neural and vascular dysfunction in early diabetes are caused primarily by increased NADHc, which fuels superoxide production by NADH-driven oxidases. Antioxid. Redox Signal.

AB - These experiments were undertaken to assess the importance of cytoplasmic (c) sorbitol oxidation versus mitochondrial (m) pyruvate oxidation in mediating neural and vascular dysfunction attributable to hyperglycemia in diabetic rats. Increased oxidation of sorbitol is coupled to enzymatic reduction of free oxidized NAD +c to reduced NADHc, manifested by an increased ratio of NADH to NAD +c. Likewise, increased oxidation of pyruvate is coupled to reduction of NAD +m to NADHm, which increases the NADH/NAD +m ratio. Specific inhibitors of sorbitol production or sorbitol oxidation normalized: increased diabetic nerve NADH/NAD +c, impaired nerve-conduction velocity, and vascular dysfunction in sciatic nerve, retina, and aorta; however, they had little or no impact on increased NADH/NAD +m. These observations provide, for the first time, strong in vivo evidence for the primacy of sorbitol oxidation versus. pyruvate oxidation in mediating the metabolic imbalances, impaired nerve conduction, and vascular dysfunction evoked by diabetes. These findings are consistent with (a) the fact that oxidation of sorbitol produces "prooxidant" NADHc uncoupled from subsequent production of "antioxidant" pyruvate required for reoxidation of NADHc to NAD +c by lactate dehydrogenase, and (b) the hypothesis that neural and vascular dysfunction in early diabetes are caused primarily by increased NADHc, which fuels superoxide production by NADH-driven oxidases. Antioxid. Redox Signal.

UR - http://www.scopus.com/inward/record.url?scp=71549149395&partnerID=8YFLogxK

U2 - 10.1089/ars.2009.2502

DO - 10.1089/ars.2009.2502

M3 - Journal article

C2 - 19624259

AN - SCOPUS:71549149395

VL - 12

SP - 39

EP - 51

JO - Antioxidants & Redox Signaling

JF - Antioxidants & Redox Signaling

SN - 1523-0864

IS - 1

ER -