Tamm Horsfall glycoprotein in diabetes mellitus: abnormal chemical composition and colloid stability.
Tamm Horsfall glycoprotein (THP) was isolated, using sodium chloride precipitation technique, from 24-h urine of 19 non-proteinuric insulin-dependent diabetics and 19 matched controls. Tamm Horsfall glycoprotein was pure, as judged by PAGE electrophoresis, by Ouchterlony double diffusion against anti-THP or anti-albumin antibodies, and by isoelectric focusing. Content of carbohydrates (gas-chromatography), amino acids or amino sugars (AA-analyser), N-acetylneuraminic acid (thiobarbituric acid method) and lysyl-bound glucose (furosine method) were determined and showed the following abnormalities: THP of diabetics had significantly higher glucose content (d: 2.55 +/- 0.66 g 100 g-1 THP; CO: 0.99 +/- 0.23; P less than 0.05) and increased lysyl-bound glucose, but diminished N-acetyl-neuraminic acid content (3.54 +/- 0.25 vs. 4.96 +/- 0.15; P less than 0.01) with no significant differences of amino acids or amino sugars. Low N-acetyl-neuraminic acid content was paralleled by reduced surface charge density of THP, as revealed by polyelectrolyte titration. No abnormality of the protein core was revealed by amino acid analysis and by probing reactivity to seven different monoclonal antibodies to human THP. Altered colloid stability, i.e. greater precipitation of THP of diabetic patients, was demonstrated by laser nephelometry. The data are consistent with abnormal post-translational modification of THP in diabetes.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D003102:Colloids; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D004573:Electrolytes / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007120:Immunochemistry; D005779:Immunodiffusion; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009088:Mucoproteins / Q000652:urine*; D009391:Nephelometry and Turbidimetry; D058949:Uromodulin
D000911:Antibodies, Monoclonal; D003102:Colloids; D004573:Electrolytes; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin