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Differentiating between effects of streptozotocin per se and subsequent hyperglycemia on renal function and metabolism in the streptozotocin-diabetic rat model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
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2004 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 20, no 6, 452-459 p.Article in journal (Refereed) Published
Abstract [en]


The animal model with streptozotocin (STZ)-induced diabetes mellitus is associated with progressive renal disturbances. The aim of this study was to differentiate between toxic effects of STZ and the effect of hyperglycemia. Previous studies have been limited to investigating the influence of STZ on glomerular filtration rate (GFR), albuminuria and renal morphology. The present study presents a new approach when transplanting beta-cells to cure the STZ-treated animals and extends the evaluation to include both renal function and oxygen metabolism.


Animals were allocated to three groups: control animals, STZ-diabetic animals and animals rendered diabetic with an injection of STZ, followed by immediate syngeneic transplantation of approximately 1000 pancreatic islets into the splenic parenchyma. This latter procedure reversed the hyperglycemia induced by STZ. Renal function was evaluated from GFR and urinary albumin and protein leakage, while regional renal blood flow was determined using a laser-Doppler technique and oxygen tension measured with Clark-type electrodes.


In diabetic animals, GFR increased, renal oxygen tension decreased and renal hypertrophy occurred, along with urinary leakage of protein, including albumin. Early transplantation of pancreatic islets to STZ-treated animals prevented the development of all these changes, except for proteinuria. However, an analysis of urinary protein content revealed that albuminuria was preventable by islet transplantation.


We conclude that the urinary protein leakage in this animal model is at least partly due to direct toxic effects of STZ, whereas the other renal changes investigated in this study are due to the long-term diabetic condition.

Place, publisher, year, edition, pages
2004. Vol. 20, no 6, 452-459 p.
Keyword [en]
Animals, Diabetes Mellitus; Experimental/complications/metabolism/pathology/*physiopathology/surgery, Glomerular Filtration Rate, Hyperglycemia/*physiopathology, Islets of Langerhans Transplantation, Kidney/*drug effects/metabolism/pathology/*physiopathology, Male, Natriuresis, Oxygen/metabolism, Potassium/urine, Proteinuria/etiology, Rats, Rats; Wistar, Research Support; Non-U.S. Gov't, Streptozocin/*pharmacology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-91845DOI: 10.1002/dmrr.472PubMedID: 15386825OAI: oai:DiVA.org:uu-91845DiVA: diva2:164706
Available from: 2004-05-03 Created: 2004-05-03 Last updated: 2013-05-16Bibliographically approved
In thesis
1. Diabetes-induced Alterations in Renal Microcirculation and Metabolism
Open this publication in new window or tab >>Diabetes-induced Alterations in Renal Microcirculation and Metabolism
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diabetes-induced renal complications, i.e. diabetes nephropathy, are a major cause of morbidity and mortality. The exact mechanism mediating the negative influence of hyperglycaemia on renal function is unclear, although several hypotheses have been postulated. Glucose-induced excessive formation of reactive oxygen species (ROS) and increased glucose flux through the polyol pathway are two major mechanisms that have recently gained increasing support. In order to investigate the development of hyperglycaemia-induced renal alterations further, it is of great importance to use an animal model in agreement with the pathological development in diabetic patients.

The aims of these investigations were to evaluate the streptozotocin (STZ)-diabetic Wistar Furth rat as a model for human diabetic nephropathy and to investigate involvement of ROS and the polyol pathway in development of diabetes-induced renal alterations.

The used STZ-diabetic animal model displayed several similarities with the progression of human disease, including initial hyperfiltration and albuminuria. However, the observed proteinuria could be partly linked to the STZ treatment per se, making the use of this animal model less suitable for research concerning diabetes-induced urinary protein leakage.

The diabetic state induced numerous alterations in renal function and metabolism, including increased oxygen consumption, decreased renal oxygen tension (pO2), and altered lactate/pyruvate ratio. These renal alterations were preventable by daily treatment with either a radical scavenger (α-tocopherol) or an aldose reductase inhibitor (AL-1576).

In separate experiments the influence of nitric oxide (NO) on renal blood perfusion and pO2 was investigated. The diabetic animals displayed a larger increase in renal NO activity after injecting the NO substrate L-arginine compared to non-diabetic animals, suggesting substrate limitation of the nitric oxide synthase during chronic hyperglycaemia.

In conclusion, the results from these investigations show that both ROS and the polyol pathway are involved in the development of diabetes-induced renal alterations in the STZ- diabetic Wistar Furth rat.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 45 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1358
Physiology, diabetes mellitus, kidney, nephropathy, oxygen tension, haemodynamic, nitric oxide, oxygen consumption, radical oxygen species, polyol pathway, Fysiologi
National Category
urn:nbn:se:uu:diva-4285 (URN)91-554-5985-4 (ISBN)
Public defence
2004-05-24, Sal IV, Universitetshuset, Uppsala, 09:15
Available from: 2004-05-03 Created: 2004-05-03Bibliographically approved

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