How the sialylation level of serum N-acetyl-beta-D-glucosaminidase A form in Type 1 diabetes mellitus influences their activity?

It was verified that the serum N-acetyl-beta-D-glucosaminidase (NAG) activity is elevated in diabetes, but there are no reports about changes in the sialic acid (SA) content in the carbohydrate parts of the NAG A form and its influence on the total changes in NAG activity in type 1 diabetes mellitus patients with and without secondary complications. The NAG A form was isolated from the serum of 81 insulin-dependent diabetes mellitus (IDDM) patients with and without secondary complications (retinopathy, polyneuropathy and nephropathy) and 25 healthy persons, and purified and characterised. The content of alpha-2,6-bound SA, the isoenzyme patterns of the purified A form, and the total NAG and A form activities were determined. In all diabetic groups, the sialylation levels of the A form were 2-3.5 times lower compared to control, while their acidities (fractions with pI 4.25-5.1) increased, particularly with progression of secondary complications. Total serum NAG activities and percentages of A form were significantly higher (P lt 0.001) in all diabetic groups and negatively correlated with the alpha-2,6-bound SA content of the A form. In addition, they decreased as secondary diabetic complications became more complex. The observed changes could be the consequence of structural changes in the A form due to significant increases in its acidity, i.e., negative charge, which originated from groups other than SA

Serum N-acetyl-beta-D-glucosaminidase profiles in type 1 diabetes secondary complications: Causes of changes and significance of determination

The connection between changes in the activity of serum N-acetyl-beta-D-glucosaminidase (NAG, E.C.3.2.1.30) and iso-enzymes and degree of secondary complications was analyzed in four groups of type 1 diabetic patients (n=69): without complications (n=22); with retinopathy (n=16); with retinopathy and polyneuropathy (n= 13), and with retinopathy, neuropathy, and nephropathy (n=18). In all groups statistically significant higher (P lt 0.001) percent fraction of A form (83.84 +/- 6.09, 84.37 +/- 5.74, 81.76 +/- 6.02, 76.37 +/- 7.38%, resp.) and lower (P lt 0.001, P lt 0.01) fraction of B form (15.87 +/- 5.65, 15.66 +/- 5.74, 18.33 +/- 5.98, 23.63 +/- 7.38, resp.) in total NAG compared with the control (A = 69.38 +/- 4.79%, B = 30.61 +/- 4.78%) were found. The differences in A as well as B forms between diabetic groups were not statistically significant. Significant strong positive correlations between total NAG and glycemia (0.494-0.623), total NAG and A form (0.934-0.966), and A form and glycemia (0.512-0.638) were found in all groups. No correlation was found between the fractions of B and A forms, except in the fourth group. The A form of diabetic patients in the fourth group was more acidic compared with the control and other diabetic groups. It was concluded that the changes in serum NAG and isoenzymic profiles in diabetes are the consequence of its increased exocytose, especially of the A form, in hyperglycemia and posttranslational modifications of iso-enzymes. The total activity of serum NAG and iso-enzymic profiles cannot be used for monitoring the development and distinction of type 1 diabetes secondary complications