Document Detail


Effect of an aldose reductase inhibitor on type IV collagen production by human endothelial cells cultured in high glucose.
MedLine Citation:
PMID:  8781759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diabetic microangiopathy is characterized by a thickening of capillary basement membranes associated with type IV collagen accumulation. An increase in type IV collagen content of the aortic wall is also observed in macroangiopathy. In order to analyse the importance of the polyol pathway in the development of the collagen metabolism alterations seen in diabetic angiopathy and their prevention by aldose reductase inhibitors, we have studied the effects of sorbinil on the high glucose-induced stimulation of type IV collagen biosynthesis in human umbilical vein endothelial cells. Primary cultures were exposed to high glucose (16.7 mmol/l), with and without 0.11 mmol/l sorbinil, for 3 or 6 days after beginning of confluence. We measured the soluble type IV collagen secreted into the culture medium and the insoluble type IV collagen accumulated in the extracellular matrix and cells, by ELISA. We also studied [14C]proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. High glucose decreased the number of cells and increased the amount of type IV collagen in the culture supernatant and in the extracellular matrix and cell fraction. It also increased proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. Sorbinil corrected all these high glucose-induced alterations. The corrective effects of sorbinil on the proliferation and on type IV collagen metabolism of endothelial cells cultured in high glucose may be attributed to prevention of polyol pathway dysregulation.
Authors:
A Bakillah; A M Grigorova-Borsos; R Guillot; P Urios; M Sternberg
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetologia     Volume:  39     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-12-05     Completed Date:  1996-12-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  641-8     Citation Subset:  IM    
Affiliation:
Equipe de Recherches sur la Biochimie et la Pharmacologie des Vaisseaux et du Rein, Faculté de Médecine Broussais-Hôtel-Dieu, U.F.R. Biomédicale des Saints-Pères, Université de Paris V & VI, Paris.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Reductase / antagonists & inhibitors*
Animals
Carbon Radioisotopes / diagnostic use
Cell Survival / drug effects
Cells, Cultured
Collagen / biosynthesis*,  drug effects,  immunology
Culture Media, Serum-Free
Diabetic Angiopathies / etiology
Dose-Response Relationship, Drug
Endothelium, Vascular / cytology,  drug effects*,  metabolism
Enzyme Inhibitors / pharmacology*
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix / chemistry
Glucose / pharmacology*
Humans
Imidazoles / pharmacology*
Imidazolidines*
Osmolar Concentration
Proline / analysis,  metabolism
Proteins / metabolism,  secretion
Umbilical Veins / cytology
Chemical
Reg. No./Substance:
0/Carbon Radioisotopes; 0/Culture Media, Serum-Free; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Imidazolidines; 0/Proteins; 147-85-3/Proline; 50-99-7/Glucose; 68367-52-2/sorbinil; 9007-34-5/Collagen; EC 1.1.1.21/Aldehyde Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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