AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 290: E1057-E1067, 2006. First published December 27, 2005; doi:10.1152/ajpendo.00323.2005
0193-1849/06 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
290/6/E1057    most recent
00323.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ola, M. S.
Right arrow Articles by LaNoue, K. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ola, M. S.
Right arrow Articles by LaNoue, K. F.

Analysis of glucose metabolism in diabetic rat retinas

M. Shamsul Ola,1 Deborah A. Berkich,1 Yuping Xu,1 M. Todd King,2 Thomas W. Gardner,3 Ian Simpson,4,* and Kathryn F. LaNoue1,*

Departments of 1Cellular and Molecular Physiology, 4Neural and Behavioral Sciences, and 3Ophthalmology, Pennsylvania State College of Medicine, Hershey, Pennsylvania; and 2Laboratory of Metabolic Control, The National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland

Submitted 19 July 2005 ; accepted in final form 13 December 2005

This study was conceived in an effort to understand cause and effect relationships between hyperglycemia and diabetic retinopathy. Numerous studies show that hyperglycemia leads to oxidative stress in the diabetic retinas, but the mechanisms that generate oxidative stress have not been resolved. Increased electron pressure on the mitochondrial electron transfer chain, increased generation of cytosolic NADH, and decreases in cellular NADPH have all been cited as possible sources of reactive oxygen species and nitrous oxide. In the present study, excised retinas from control and diabetic rats were exposed to euglycemic and hyperglycemic conditions. Using a microwave irradiation quenching technique to study retinas of diabetic rats in vivo, glucose, glucose-derived metabolites, and NADH oxidation/reduction status were measured. Studying excised retinas in vitro, glycolytic flux, lactate production, and tricarboxylic acid cycle flux were evaluated. Enzymatically assayed glucose 6-phosphate and fructose 6-phosphate were only slightly elevated by hyperglycemia and/or diabetes, but polyols were increased dramatically. Cytosolic NADH-to-NAD ratios were not elevated by hyperglycemia nor by diabetes in vivo or in vitro. Tricarboxylic acid cycle flux was not increased by the diabetic state nor by hyperglycemia. On the other hand, small increases in glycolytic flux were observed with hyperglycemia, but glycolytic flux was always lower in diabetic compared with control animals. An observed decrease in activity of glyceraldehyde-3-phosphate dehydrogenase may be partially responsible for slow glycolytic flux for retinas of diabetic rats. Therefore, it is concluded that glucose metabolism, downstream of hexokinase, is not elevated by hyperglycemia or diabetes. Metabolites upstream of glucose such as the sorbitol pathway (which decreases NADPH) and polyol synthesis are increased.

diabetic retinopathy; hyperglycemia; reactive oxygen species; mitochondria; glycolysis; polyols


Address for reprint requests and other correspondence: K. F. LaNoue, Dept. of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, P.O. Box 850, Hershey, PA 17033 (e-mail: klanoue{at}psu.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.