hydroxylysine and Diabetic-Angiopathies

Topics: Amino Acids; Basement Membrane; Diabetic Angiopathies; Diabetic Nephropathies; Glycoproteins; Humans; Hydroxylysine; Kidney Glomerulus; Macromolecular Substances; Models, Chemical

Topics: Animals; Basement Membrane; Carbohydrate Metabolism; Cattle; Collagen; Diabetic Angiopathies; Fibroblasts; Galactose; Glucose; Glycoproteins; Humans; Hydroxylysine; Hydroxyproline; Insulin; Kidney Glomerulus; Lysine; Oligosaccharides; Rats

In incubation experiments with isolated glomeruli, an increased synthesis of protein and basement membranes was detected in streptozotocin-diabetic rats compared to metabolically healthy controls. Chemical analysis of isolated basement membranes and incorporation studies did not give any indication of enhanced hydroxylation of lysine in the diabetic membrane. Different glucose concentration in the incubation medium and insulin in vitro did not influence protein and basement membrane synthesis of non-diabetic glomeruli. On the other hand, in diabetic glomeruli the synthetic activity depends on glucose concentration. Insulin had a stimulatory effect on protein and basement membrane synthesis diminished at lower glucose concentration and did not inhibit the increased synthetic activity demonstrated at higher glucose concentration. Therefore, these results may be attributable to an energy deficit of incubated glomeruli and not to a lower glucose stimulation of synthesis. By treatment of diabetic rats with insulin in vivo the synthetic activity was not affected by brief normalization of blood sugar. Insulin treatment from the beginning of diabetes only lead to a normalization of protein synthesis in moderate metabolic control. On the other hand, a rise of basement membrane synthesis could only be prevented by strict metabolic control of the rats. These results show that basement membrane synthesis reacts more sensitively to the diabetic situation than overall protein synthesis. Insulin deficiency does not appear to be one of the factors directly influencing basement membrane synthesis.

Topics: Animals; Basement Membrane; Blood Glucose; Diabetic Angiopathies; Glucose; Hydroxylysine; Insulin; Kidney Glomerulus; Lysine; Protein Biosynthesis; Rats

Biochemical modifications of glomerular basement membrane (GBM) in diabetes mellitus have been investigated in human subjects. Amino acid analysis and electrophoretic study of unfractioned GBM from diabetic and non diabetic kidneys showed an increase in hydroxylysine, hydroxyproline and glycine and in the glycosylgalactosyl-hydroxylysine (G-G-H) content of diabetic GBM. A decrease in 1/2 cystine was also demonstrated in diabetes. Fractionation of GBM showed the increase in G-G-H observed on unfractioned GBM to reflect a quantitative increase of the "collagen" fraction in diabetes, the amino acid composition of this fraction remaining unchanged. The decrease in 1/2 cystine demonstrated on unfractioned GBM was located in the non collagenous fractions of this structure.

Topics: Amino Acids; Basement Membrane; Collagen; Diabetic Angiopathies; Glycine; Hexoses; Humans; Hydroxylysine; Hydroxyproline; Kidney Glomerulus; Sialic Acids