Reduced trypsin binding capacity of alpha 2-macroglobulin in diabetes.
The plasma proteinase inhibitor, alpha 2-macroglobulin, is usually elevated in diabetes. The trypsin binding capacity and the concentration of alpha 2-macroglobulin in 90 diabetics sera were compared with 30 age- and sex-matched normal sera. The mean alpha 2-macroglobulin concentration determined by radial immunodiffusion was 313 mg/dl for the diabetics as compared to 240 mg/dl for the healthy subjects (significantly higher, p less than 0.01). The mean of the ratio, mol trypsin bound/mol alpha 2-macroglobulin (molar binding ratio) for the Type I diabetics (n = 54), 0.82, was significantly lower than the mean of the healthy subjects, 0.87, or the mean of the Type II diabetics, 0.87. No relationship between the molar binding ratios and the levels of glycosylated hemoglobin was found. The alpha 2-macroglobulin was isolated from the plasma of 11 Type I diabetics and 7 normals. The maximum molar trypsin binding capacities of the diabetic alpha 2-macroglobulin were significantly lower. The mean for the diabetic alpha 2-macroglobulin was 1.72 vs. 1.97 for the normal alpha 2-macroglobulin. These results indicate that the trypsin binding function of alpha 2-macroglobulin is moderately impaired in diabetes. No differences were found in the extent of proteolytic cleavage of the 'bait region' of diabetic alpha 2-macroglobulin, autolytic cleavage or the methylamine reaction at the thiolester site between diabetic and normal alpha 2-macroglobulin. Nonenzymatic glucosylation of normal alpha 2-macroglobulin did not lower the trypsin binding capacity. The nature of the modification of alpha 2-macroglobulin leading to reduced trypsin binding capacity or the physiological significance is not yet known.
R C
RC
Roberts
P K
PK
Hall
T F
TF
Nikolai
A K
AK
McKenzie
D000328:Adult; D003920:Diabetes Mellitus / Q000097:blood*; D010450:Endopeptidases / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D007525:Isoelectric Focusing; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D011487:Protein Conformation; D014357:Trypsin / Q000378:metabolism* / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000032:analysis / Q000378:metabolism*
D010450:Endopeptidases; D005947:Glucose; D006442:Glycated Hemoglobin; D008744:Methylamines; D014357:Trypsin; D000511:alpha-Macroglobulins; C027451:methylamine