Modification of the glomerular basement membrane in sucrose-fed and streptozotocin-diabetic rats

Abstract

Rats were fed on diets containing either sucrose or starch as the carbohydrate component (55%) for eight months. Diabetes was induced in animals of both groups by injecting streptozotocin (50 mg/kg body weight). Diabetic rats failed to gain weight, had enlarged kidneys, polyuria and elevated blood glucose levels. Starch and sucrose fed rats gained weight normally and had normal blood glucose levels. Sucrose fed rats had enlarged kidneys. Regional thickening of the glomerular basement membrane was present in sucrose-fed and diabetic rats but not in starch-fed controls. Glomerular basement membrane isolated from pooled kidney cortices from rats in the different experimental groups were analysed for amino acid, disaccharide and hexosamine content. Hydroxylysine (9 to 20%), hydroxyproline (21 to 24%), disaccharide (27%) and hexosamine (26%) were increased in membranes insolated from the three experimental groups, compared with starch-fed non-diabetic controls. An increase in low molecular weight components of the glomerular basement membrane of sucrose-fed and diabetic rats was observed using electrophoresis in sodium dodecyl sulphate. Significantly higher (p < 0.001) glucosyltransferase activity was present in kidney supernatants prepared from sucrose-fed (1050 +/- 60 nmol/2h/kidney) compared to starch-fed rats (510 +/- 40 nmol/2h/kidney). Sucrose feeding induces changes similar to those found in diabetes and the induction of diabetes made little difference over the feeding of sucrose alone.

Modulating Influence of Barley on the Altered Metabolism of Glucose and of Basement Membranes in the Diabetic Rat

“…In support of this view it was noted that in genetically diabetic mice with both hyper glycaemia and hyperinsulinaemia, no in crease in serum basement membrane antigens was found [9]. Furthermore, the long-term feeding of sucrose that lead to the develop ment of changes in the glomerular basement membrane similar to those found in diabetic rats [16] did not affect the blood glucose con centration.…”

“…The prolonged (8 months) feeding of rats with sucrose, compared with starch, has been found to cause enlargement of the kidneys, and regional thickening of the glomerular basement membrane, with alterations in com position [16]. In the present study, however, which was of shorter duration (2 months) no significant differences in any of the measure-merits made were detected between the su crose-fed and barley-fed control groups.…”

Composition and Biosynthesis of Glomerular Basement Membrane in Rats Fed Diets Rich in Sucrose

“…The presence of microaneurysm of the capillary bed of the retina [7] and thickening of the GBM [10] in SU rats indicates that dietary SU is capable of inducing two of the prime manifestations of diabetes. Of partic ular interest is the finding that GBM thick ening occurs with normal blood sugar levels in SU rats, while elevated blood sugar levels are present in diabetic rats.…”

“…The glucosyl transferase activity of renal cortial homogenates prepared in 0.15 M Tris-acetate buffer. pH 6.8, containing 0.002 A/-mercaptocthanol was de termined using deglucosylated rat GBM as substrate [10]. GBM (2.5 mg/ml) was solubilised in 1% sodium dodecyl sulphate (SDS) and 1% 2-mercaptoethanol and the soluble components characterised by SDS poly acrylamide gel electrophoresis in 5% gels [28].…”

“…Subsequent work demonstrated that these changes were associated with the ele vation of the activity of N-acetyl-P-Z)-glucosaminidase in urine [8], which was indica tive of the presence of renal damage since elevation of this enzyme in urine is asso ciated with renal tubular damage [9]. Irreg ular thickening of GBM also occurs in SU fed rats [10], a feature which is characteristic of the nephropathy of diabetes [11] and has been demonstrated in alloxan [12] and strep tozotocin [13] diabetic rats.…”