Immunocytochemical distribution of endogenous albumin and immunoglobulins in the glomerular wall of the sucrose-fed "Cohen" diabetic rat.
Endogenous circulating albumin and immunoglobulin G (IgG) molecules were revealed with high resolution over the glomerular wall of renal tissue from normoglycemic and sucrose-fed hyperglycemic Cohen rats applying the protein A-gold immunocytochemical approach. Due to the length of the experiment, the hyperglycemic animals demonstrated only minor renal morphological alterations. In spite of this, labelling for albumin and immunoglobulins in the glomerular wall showed significant differences between the normoglycemic and hyperglycemic animals. In the former, the labelings were restricted to the endothelial side of the glomerular basement membrane, while in the latter, the labelings were distributed throughout the entire thickness of the basement membrane. In addition, the hyperglycemic animals display some labelling associated with the slit diaphragms between podocytes and in the urinary space. Numerous lysosomal structures present in podocytes and mesangial cells of the hyperglycemic animals were intensely labeled for albumin and IgGs, reflecting a reabsorption activity. Dense deposits labeled for IgGs were found in the glomerular wall and mesangial regions of hyperglycemic animals corresponding to depositions of immune-complexes. These results demonstrated that in hyperglycemic conditions induced by environmental factors such as the diet, the permselectivity of the glomerular basement membrane is lost; proteins such as albumin and IgGs are not restricted by the endothelial side of the basement membrane and cross the glomerular wall leading to proteinuria. The loss of selective permeability properties of the glomerular basement membrane was found to precede the morphological changes occurring in the glomerular wall during diabetes.
Livni
N
N
Department of Anatomy, Universite de Montreal, Quebec, Canada.
Bendayan
M
M
Gingras
D
D
Rosenmann
E
E
Cohen
A M
AM
D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005260:Female; D007136:Immunoglobulins / Q000032:analysis*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D011236:Prediabetic State / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000032:analysis*; D013395:Sucrose / Q000494:pharmacology*
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007136:Immunoglobulins; D007328:Insulin; D012709:Serum Albumin; D013395:Sucrose