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Evaluation of the impact of diabetes on retinal metabolites by NMR spectroscopy

Santiago, A. R. ; Garrido, M. J. ; Cristóvão, A. J. ; Duarte, J. M.N. LU orcid ; Carvalho, R. A. and Ambrósio, A. F. (2010) In Current Eye Research 35(11). p.992-1001
Abstract

Purpose/Aim of the study: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults in developed countries. Changes in metabolites and in metabolic pathways of the retina caused by hyperglycemia may compromise the physiology of the retina. Using nuclear magnetic resonance (NMR) spectroscopy, we aimed to investigate the effect of diabetes on the levels of intermediate metabolites in rat retinas and the metabolic pathways that could be affected. Materials and Methods: Diabetes was induced in male Wistar rats with a single injection of streptozotocin (65mg/Kg, i.p.). Metabolic alterations were analyzed in streptozotocin-induced diabetic rat retinas by 1H NMR spectroscopy. Glucose uptake was measured with... (More)

Purpose/Aim of the study: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults in developed countries. Changes in metabolites and in metabolic pathways of the retina caused by hyperglycemia may compromise the physiology of the retina. Using nuclear magnetic resonance (NMR) spectroscopy, we aimed to investigate the effect of diabetes on the levels of intermediate metabolites in rat retinas and the metabolic pathways that could be affected. Materials and Methods: Diabetes was induced in male Wistar rats with a single injection of streptozotocin (65mg/Kg, i.p.). Metabolic alterations were analyzed in streptozotocin-induced diabetic rat retinas by 1H NMR spectroscopy. Glucose uptake was measured with 2-deoxy-d-[1-3H] glucose. Lactate production was evaluated by 1H NMR spectroscopy using [U-13C]glucose. Results: Tissue levels of several metabolic intermediates were quantified, but no significant changes in the levels of most metabolites were detected, with the exceptions of glucose, significantly increased, and lactate, significantly reduced in diabetic rat retinas, as compared to age-matched controls. The cytosolic redox ratio, indirectly evaluated by lactate-to-pyruvate ratio, was significantly reduced in diabetic rat retinas, as well as glucose uptake. Parallel studies demonstrated that lactate production rates were significantly diminished, suggesting a reduction in the glycolytic flux. Conclusions: These results suggest that diabetes may significantly decrease glycolysis in the retina since higher intracellular glucose levels do not translate into higher intracellular lactate levels or into higher rates of lactate production. These changes may alter the normal functioning of the retina during diabetes and may contribute for vision loss in DR.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetes, Diabetic retinopathy, Glucose uptake, Glycolysis, Lactate, Nuclear magnetic resonance, Streptozotocin
in
Current Eye Research
volume
35
issue
11
pages
992 - 1001
publisher
Taylor & Francis
external identifiers
  • pmid:20958188
  • scopus:77958505485
ISSN
0271-3683
DOI
10.3109/02713683.2010.500113
language
English
LU publication?
no
additional info
Funding Information: This work was supported by the Foundation for Science and Technology, Portugal (POCTI/CBO/38545/01 and POCTI/CBO/38611/01) and FEDER.
id
d69ea5d0-1b52-48cc-929a-f59b6fa5024c
date added to LUP
2024-01-08 10:55:13
date last changed
2024-01-08 11:29:24
@article{d69ea5d0-1b52-48cc-929a-f59b6fa5024c,
  abstract     = {{<p>Purpose/Aim of the study: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults in developed countries. Changes in metabolites and in metabolic pathways of the retina caused by hyperglycemia may compromise the physiology of the retina. Using nuclear magnetic resonance (NMR) spectroscopy, we aimed to investigate the effect of diabetes on the levels of intermediate metabolites in rat retinas and the metabolic pathways that could be affected. Materials and Methods: Diabetes was induced in male Wistar rats with a single injection of streptozotocin (65mg/Kg, i.p.). Metabolic alterations were analyzed in streptozotocin-induced diabetic rat retinas by <sup>1</sup>H NMR spectroscopy. Glucose uptake was measured with 2-deoxy-d-[1-<sup>3</sup>H] glucose. Lactate production was evaluated by <sup>1</sup>H NMR spectroscopy using [U-<sup>13</sup>C]glucose. Results: Tissue levels of several metabolic intermediates were quantified, but no significant changes in the levels of most metabolites were detected, with the exceptions of glucose, significantly increased, and lactate, significantly reduced in diabetic rat retinas, as compared to age-matched controls. The cytosolic redox ratio, indirectly evaluated by lactate-to-pyruvate ratio, was significantly reduced in diabetic rat retinas, as well as glucose uptake. Parallel studies demonstrated that lactate production rates were significantly diminished, suggesting a reduction in the glycolytic flux. Conclusions: These results suggest that diabetes may significantly decrease glycolysis in the retina since higher intracellular glucose levels do not translate into higher intracellular lactate levels or into higher rates of lactate production. These changes may alter the normal functioning of the retina during diabetes and may contribute for vision loss in DR.</p>}},
  author       = {{Santiago, A. R. and Garrido, M. J. and Cristóvão, A. J. and Duarte, J. M.N. and Carvalho, R. A. and Ambrósio, A. F.}},
  issn         = {{0271-3683}},
  keywords     = {{Diabetes; Diabetic retinopathy; Glucose uptake; Glycolysis; Lactate; Nuclear magnetic resonance; Streptozotocin}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{992--1001}},
  publisher    = {{Taylor & Francis}},
  series       = {{Current Eye Research}},
  title        = {{Evaluation of the impact of diabetes on retinal metabolites by NMR spectroscopy}},
  url          = {{http://dx.doi.org/10.3109/02713683.2010.500113}},
  doi          = {{10.3109/02713683.2010.500113}},
  volume       = {{35}},
  year         = {{2010}},
}