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[Changes in collagen type IV metabolism in diabetes]
M Sternberg1, A M Grigorova-Borsos, R Guillot
1Université de Paris V et VI, Département de Biochimie, Faculté de Médecine.
Comptes Rendus Des Seances De La Societe De Biologie Et De Ses Filiales
|January 1, 1993
Summary
In diabetes mellitus, increased type IV collagen production and accumulation in basement membranes contribute to complications. Aldose reductase inhibitors show potential in preventing this pathological collagen overproduction.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Context:
- Diabetes Mellitus is associated with significant microvascular complications, often linked to basement membrane abnormalities.
- Type IV collagen is a key structural component of basement membranes, and its dysregulation is implicated in diabetic nephropathy and other pathologies.
Purpose:
- To investigate the mechanisms underlying type IV collagen overproduction and accumulation in Diabetes Mellitus.
- To explore the role of aldose reductase inhibitors and high glucose concentrations in modulating type IV collagen metabolism.
Summary:
- Elevated alpha 1(IV) procollagen mRNA and protein lead to type IV collagen accumulation and basement membrane thickening in diabetes.
- Aldose reductase inhibitors and potentially TGF-beta influence type IV collagen synthesis.
- Posttranslational glycation of type IV collagen increases advanced glycation end-products, reducing extractability and increasing basement membrane thickening.
- High glucose diminishes endothelial cell type IV collagenase activity, suggesting decreased catabolism in diabetes.
Impact:
- Understanding these pathways provides insights into diabetic complications and potential therapeutic targets.
- Aldose reductase inhibitors demonstrate a protective effect against basement membrane thickening.
- Modulating type IV collagen synthesis and degradation may offer novel strategies for managing diabetic microvascular disease.