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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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| 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. |
| format | Article |
| id | doaj-art-8c7c76c039e9486c9fad68ff8e598838 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| 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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