Possible genetic defects in regulation of glycosaminoglycans in patients with diabetic nephropathy
- Steno Memorial Hospital, Gentofte (Denmark)
The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of (2H) glucosamine and (35S) sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of (3H) glucosamine into HA, CS + DS, and HS and (35S) sulfate into CS + DS and HS were not significantly different between the three groups. However, the fractional incorporation of (3H)glucosamine into HS was significantly reduced in diabetic patients with nephropathy compared with control subjects. This was the case not only when related to the total amount of GAGs (P = 0.014) but also when related to HA (P = 0.014). No significant difference was seen between control subjects and normoalbuminuric diabetic patients. The degree of N-sulfation of HS was not significantly different between the experimental groups. The results suggest that patients with diabetic nephropathy may suffer from deficiencies of coordinate regulation in the biosynthesis of GAG in fibroblasts, which may lead to a reduced density of HS in the extracellular matrix. If these changes reflect alterations in the biosynthesis of GAG from endothelial, myomedial, and mesangial cells, this observation may be relevant for the pathogenesis of severe diabetic complications.
- OSTI ID:
- 5396769
- Journal Information:
- Diabetes; (United States), Vol. 40:6; ISSN 0012-1797
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIABETES MELLITUS
PATHOGENESIS
GLUCOSAMINE
BIOSYNTHESIS
DEUTERIUM
FIBROBLASTS
PATIENTS
SKIN
SULFATES
SULFUR 35
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
ENDOCRINE DISEASES
EVEN-ODD NUCLEI
HEXOSAMINES
HEXOSES
HYDROGEN COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
METABOLIC DISEASES
MONOSACCHARIDES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
RADIOISOTOPES
SACCHARIDES
SOMATIC CELLS
STABLE ISOTOPES
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
550901* - Pathology- Tracer Techniques