Our research team developed a model of mild diabetes by STZ neonatal-induction. In adulthood, the rats develops mild hyperglycemia and overt renal damage: urea and serum creatinine altered in addition to other urinary parameters. However rats do not exhibit glucosuria. What are the pathophysiological mechanisms that may explain these results? Thanks
Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417415/
Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417415/
you could find microalbuminuria at early phase if you measured.
Nephron Physiol. 2007;106(2):p26-31. Epub 2007 Jun 6.
Cellular and molecular mechanisms of proteinuria in diabetic nephropathy.
Wolf G1, Ziyadeh FN.
Author information
Abstract
One of the earliest clinically detectable abnormalities in diabetic nephropathy is microalbuminuria that eventually progresses to proteinuria. The degree of proteinuria correlates with the progression of glomerulosclerosis and tubulointerstitial fibrosis. In the glomerulus, a typical podocytopathy develops that participates in the initiation of glomerulosclerosis and the accelerated plasma protein leakage across the glomerular basement membrane (GBM) into Bowman's space. Downstream into the tubular compartment, the proteinuria induces proinflammatory and profibrogenetic injury in tubular cells which can facilitate the development of interstitial fibrosis and tubular atrophy. It has long been held that hemodynamic changes and the loss of negatively charged proteoglycans in the GBM are important mediators of proteinuria. More recently, biopsy studies in humans with diabetic kidney disease have provided strong evidence that podocytes are injured very early in the course of nephropathy. This podocytopathy--which is characterized by decreased podocyte number and/or density, GBM thickening and altered matrix composition, and foot process effacement--correlates closely with the development and progression of albuminuria. Components of the diabetic milieu (high glucose, accumulation of glycated proteins, high intrarenal angiotensin II (ANG II), and hypertension-induced mechanical stress) result in activation of cytokine systems, the most important of which are transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor-A (VEGF-A). ANG II-stimulated podocyte-derived VEGF, through a novel autocrine signaling loop, appears to be a major cause of nephrin downregulation and the development of proteinuria. Nephrin is an important protein of the slit diaphragm with anti-apoptotic signaling properties. TGF-beta1 causes podocyte apoptosis and an increase in extracellular matrix deposition. As a consequence, the denuded GBM adheres to Bowman's capsule initiating the development of glomerulosclerosis. Good control of hyperglycemia and hypertension and maximal inhibition of ANG II are essential steps in preventing the development and progression of diabetic nephropathy.
Copyright 2007 S. Karger AG, Basel.
Diabetes and hypertension are serious risk factors for kidney damage. Renal endothelin - angiotensin system is involved in chronic fibrosis leading to renal failure. Have you checked the blood pressure in your experimental rats?
Here are couple of publications you may find useful:
Progression of diabetic nephropathy. Insights from cell culture studies and animal models.
http://www.ncbi.nlm.nih.gov/pubmed/10352411
Renal endothelin system in diabetes: comparison of angiotensin-converting enzyme inhibition and endothelin-A antagonism
http://www.ncbi.nlm.nih.gov/pubmed/9595522
Tausif Alam: Thank you very much for your reply. Unfortunately I do not have online access to the items. You could send them via email if you do not mind. Greetings
Leticia
The pathophysiological mechanisms that can explain the renal damage in animal models of mild diabetes can be increased ROS from chronic hyperglycemia that generates oxidative stress induces subsequently increased of protein kinase C, sorbitol, prostanoids, NF-kB, esterified fatty acids and cytokines.
Leticia,
Because of subscription related restrictions, I cannot provide you the reprints.
I believe that abstracts are freely available to everyone but full length articles is a different matter. Perhaps your institutional librarian can make some arrangements for you through inter-library loans.
Sorry!
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