engleski

Enzymes and glycosaminoglycans in diabetes

Renal damage is a serious complication of diabetes mellitus. It is estimated that death due to renal disease is 17 times more common in diabetics than in nondiabetics. When diabetic nephropathy is diagnosed by the classical methods, such as detection of proteinuria on urinalysis, or decrease in creatinine clearence, little can be done to prevent the progressive downhill course to renal failure. However, the progression of diabetic nephropathy in type I diabetic patients with microalbuminuria, which indicates the presence of glomerular involvement in early renal damage, has been reported to be retarded by good glycemic control. It would be better prognostically if diabetic nephropathy can be detected at an even earlier stage, before the appearance of microalbuminuria, so that intervention could be reverse the process, or even prevent the onset of nephropathy altogether. Recent studies have demonstrated that there is also a tubular component to renal complications of diabetes, as shown by the detection of renal tubular proteins and enzymes in the urine. In fact, tubular involvement may precede glomerular involvement, as several of these tubular proteins and enzymes are detectable even before the appearance of microalbuminuria. N-acetyl-ƒŇ-D-glucosaminidase (NAG) is the most widely assayed lysosomal enzyme for the detection of renal disease. This is attributed in part to its relative stability in urine, and the fact that its high molecular weight precludes its filtration through the glomerulus. Urine NAG excretion is associated with glycemic control. It was found that the difference in the urinary excretion of NAG between Type I and type Ii diabetic patients was small and not significant. In diabetes, there is a decrease in glycosaminoglycans (heparan sulfate, HS) which is as proteoglycan (HS-PG) component of the mesangial matrix and glomerular basement membrane. The decrease was demonstrated in tissue culture, animal studies and in human kidney. The loss of HS-PG from glomerular cellular matrix was attributed to hyperglycemia. This loss results in an alteration of the charge-selective properties of glomerular capillaries, and may contribute in part to the cause of proteinuria. Dietary and pharmacological intervention in diabetes mellitus have largely succeeded in controlling the acute features of the illness, but the late sequel of diabetes remain a major threat to health and life. In majority of the diabetic patients, even in some whose disease is apparently well controlled, plasma glucose rises into the pathological range especially after meals, giving periods of exposure to hyperglycemia, associated with the development of late complications. Acarbose inhibits the enzyme alpha glucosidase, located in the microvilli of the wall of the ileum. Inhibition of this enzyme dampens the surge of postprandial glycemia by delaying the digestion and absorption of complex carbohydrates. This attenuation of dietary carbohydrate-induced postprandial hyperglycemia may retard the development of diabetic complications.

diabetic nephropathy; type I diabetes; N.-acetyl-beta-D-glucosaminidase; proteoglycans; glycosaminoglycans

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