Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy

Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin- diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes.

[1]  M. Cohen,et al.  Renal glomerular collagen synthesis in streptozotocin diabetes. Reversal of increased basement membrane synthesis with insulin therapy. , 1977, Biochimica et biophysica acta.

[2]  R. Spiro,et al.  Studies on the metabolism of the renal glomerular basement membrane. Turnover measurements in the rat with the use of radiolabeled amino acids. , 1977, The Journal of biological chemistry.

[3]  S. Darby,et al.  Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes. , 1977, British medical journal.

[4]  M. Cohen,et al.  Evidence for heterogeneous origin of glomerular basement membrane. , 1977, Biochemical and biophysical research communications.

[5]  R. Kikkawa,et al.  Size and weight of glomeruli isolated from human diabetic and nondiabetic kidneys. , 1977, The Journal of laboratory and clinical medicine.

[6]  M. P. Cohen,et al.  Effect of diabetes and insulin on rat renal glomerular protocollagen hydroxylase activities. , 1977, Biochimica et biophysica acta.

[7]  B. Hudson,et al.  Bovine renal glomerular basement membrane. Assessment of proteolysis during isolation. , 1976, Biochemical and biophysical research communications.

[8]  P. Beisswenger.  Glomerular basement membrane: biosynthesis and chemical composition in the streptozotocin diabetic rat. , 1976, The Journal of clinical investigation.

[9]  E. J. Miller,et al.  Isolation of three collagenous components of probable basement membrane origin from several tissues. , 1976, Biochemical and biophysical research communications.

[10]  R. Spiro,et al.  Studies on the subunit composition of the renal glomerular basement membrane. , 1976, The Journal of biological chemistry.

[11]  N. Freinkel,et al.  Control and Diabetes , 1976 .

[12]  P. Bornstein,et al.  Further characterization of procollagen. Purification and analysis of the pro.alpha.1 chain of chick bone procollagen , 1975 .

[13]  C. Vogt,et al.  The Effect of Diabetes on Renal Lysine Utilization* , 1975, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[14]  M. E. Grant,et al.  The biosynthesis of basement-membrane collagen by isolated rat glomeruli. , 1975, European journal of biochemistry.

[15]  C. Vogt,et al.  Collagen synthesis and secretion by isolated rat renal glomeruli. , 1975, Biochimica et biophysica acta.

[16]  J. Daniels,et al.  Basement membrane collagen of renal glomerulus. , 1975, The Journal of biological chemistry.

[17]  M. Cohen,et al.  Glomerular protocollagen lysyl-hydroxylase activity in streptozotocin diabetes. , 1975, Biochimica et biophysica acta.

[18]  B. Hudson,et al.  Bovine Renal Glomerular Basement Membrane , 1975 .

[19]  R. Osterby,et al.  Glomerular size and structure in diabetes mellitus. I. Early abnormalities. , 1975, Diabetologia.

[20]  E. Hägg.  Glomerular basement membrane thickening in rats with long-term alloxan diabetes. A quantitative electron microscopic study. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[21]  N. A. Kefalides.  Biochemical properties of human glomerular basement membrane in normal and diabetic kidneys. , 1974, The Journal of clinical investigation.

[22]  R. Osterby.  Early phases in the development of diabetic glomerulopathy. , 1974, Acta medica Scandinavica. Supplementum.

[23]  A. Michael,et al.  Human glomerular basement membrane: chemical composition in diabetes mellitus. , 2009, Acta medica Scandinavica.

[24]  N. Blumenkrantz,et al.  An improved method for the assay of hydroxylysine. , 1973, Analytical biochemistry.

[25]  P. Beisswenger,et al.  Studies on the Human Glomerular Basement Membrane: Composition, Nature of the Carbohydrate Units and Chemical Changes in Diabetes Mellitus , 1973, Diabetes.

[26]  W. Rexroth,et al.  The metabolism of the isolated renal glomerulus and its basement membranes. , 1973, Advances in Metabolic Disorders.

[27]  N. A. Kefalides.  Structure and biosynthesis of basement membranes. , 1973, International review of connective tissue research.

[28]  R. Spiro,et al.  Fractionation of glycoprotein components of the reduced alkylated renal glomerular basement membrane. , 1972, The Journal of biological chemistry.

[29]  R. Spiro,et al.  Effect of Diabetes on the Biosynthesis of the Renal Glomerular Basement Membrane: Studies on the Glucosyltransferase , 1971, Diabetes.

[30]  G. Reaven,et al.  Effect of Experimental Diabetes Mellitus on Kidney Ribosomal Protein Synthesis , 1971, Diabetes.

[31]  P. Beisswenger,et al.  Human Glomerular Basement Membrane: Chemical Alteration in Diabetes Mellitus , 1970, Science.

[32]  R. Spiro.  Studies on the renal glomerular basement membrane. Preparation and chemical composition. , 1967, The Journal of biological chemistry.

[33]  R. Spiro.  Studies on the renal glomerular basement membrane. Nature of the carbohydrate units and their attachment to the peptide portion. , 1967, The Journal of biological chemistry.

[34]  G. Gibbs,et al.  Glomerulosclerosis in the Long-term Alloxan Diabetic Monkey , 1966, Diabetes.

[35]  P. Kimmelstiel,et al.  Studies on renal biopsy specimens, with the aid of the electron microscope. I. Glomeruli in diabetes. , 1962, American journal of clinical pathology.

[36]  M. Farquhar,et al.  Diabetic glomerulosclerosis: electron and light microscopic studies. , 1959, The American journal of pathology.

[37]  H. Bucht,et al.  Electron microscopic investigations on the glomerular lesions in diabetes mellitus (diabetic glomerulosclerosis). , 1957, Laboratory investigation; a journal of technical methods and pathology.