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  • 1
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; dextran clearance ; IgG4 ; IgG ; IgG/IgG4 selectivity index ; diabetic nephropathy ; tubular function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30–100 mg/24 h in group D2; 101–300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 μmol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of β2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 Å fractions in the range 26–64 Å) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p〈0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 Å dextran (p〈0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Heparan sulphate ; experimental diabetes ; BB rat ; albuminuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6–10 mmol/l or 10–20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10–15% following short-and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p=0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p=0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r=−0.60, p〈0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.
    Type of Medium: Electronic Resource
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