Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice

The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to fo...

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Main Authors: Y. S. Long, S. Zheng, P. M. Kralik, F. W. Benz, P. N. Epstein
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2016/8749417
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author Y. S. Long
S. Zheng
P. M. Kralik
F. W. Benz
P. N. Epstein
author_facet Y. S. Long
S. Zheng
P. M. Kralik
F. W. Benz
P. N. Epstein
author_sort Y. S. Long
collection DOAJ
description The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis.
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institution Kabale University
issn 2314-6745
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publishDate 2016-01-01
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series Journal of Diabetes Research
spelling doaj-art-8c7c76c039e9486c9fad68ff8e5988382025-02-03T01:10:55ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/87494178749417Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic MiceY. S. Long0S. Zheng1P. M. Kralik2F. W. Benz3P. N. Epstein4Department of Pediatrics, University of Louisville, Louisville, KY, USADepartment of Pediatrics, University of Louisville, Louisville, KY, USADepartment of Pediatrics, University of Louisville, Louisville, KY, USADepartment of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USADepartment of Pediatrics, University of Louisville, Louisville, KY, USAThe importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis.http://dx.doi.org/10.1155/2016/8749417
spellingShingle Y. S. Long
S. Zheng
P. M. Kralik
F. W. Benz
P. N. Epstein
Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice
Journal of Diabetes Research
title Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice
title_full Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice
title_fullStr Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice
title_full_unstemmed Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice
title_short Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice
title_sort impaired albumin uptake and processing promote albuminuria in ove26 diabetic mice
url http://dx.doi.org/10.1155/2016/8749417
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AT pmkralik impairedalbuminuptakeandprocessingpromotealbuminuriainove26diabeticmice
AT fwbenz impairedalbuminuptakeandprocessingpromotealbuminuriainove26diabeticmice
AT pnepstein impairedalbuminuptakeandprocessingpromotealbuminuriainove26diabeticmice