Authors: Francis J Descamps¹; Erik Martens¹; Florence Ballaux²; Karel Geboes²; Ghislain Opdenakker¹

Source: The Journal of Pathology, Volume 204, Number 5, December 2004 , pp. 555-561(7)

Publisher: John Wiley & Sons, Ltd.

Abstract:

Matrix metalloproteinases, in particular gelatinase B/MMP-9, are key mediators in autoimmune diseases like multiple sclerosis and rheumatoid arthritis, but their pathogenic roles in diabetes are not well established. Gelatinase B has previously been shown to be upregulated in pancreas tissue from patients with acute and chronic pancreatitis and was suggested to exacerbate diabetes by cleaving insulin. In this study, the role of gelatinase B in diabetes was investigated using two streptozotocin-induced animal models of type I diabetes. In both a hyperacute and a subacute model, gelatinase B upregulation was found to be associated with disease activity. However, gelatinase B deficiency did not significantly protect against diabetes development, and wild-type and gelatinase B-deficient animals behaved similarly in terms of -cell apoptosis or necrosis. The fact that gelatinase B was found almost exclusively as the inactive pro-enzyme in most of the streptozotocin-induced diabetic animals may explain the lack of a gelatinase B effect. On the contrary, gelatinase B was completely activated in a minority (15%) of wild-type animals. This coincided with exocrine pancreatic inflammation, as revealed by the presence of active trypsin. The discovery of in vivo activation of progelatinase B by trypsin in acute pancreatitis is extended in a model of caerulein-induced pancreatitis. In the latter model, trypsinogen activation is systematically achieved and gelatinase B is found in its active form. In conclusion, gelatinase B itself is not a causative factor but, when activated by endogenous trypsin, is a permissive factor for insulin degradation and diabetes. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: pancreatitis; diabetes; trypsin; matrix metalloproteinase-9; streptozotocin

Document Type: Research article

DOI: http://dx.doi.org/10.1002/path.1669

Affiliations: 1: Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Leuven, Belgium 2: Department of Morphology and Molecular Pathology, University of Leuven, Leuven, Belgium

Publication date: 2004-12-01

More about this publication?

• As of January 2010, this journal will no longer be available on IngentaConnect, please visit Wiley InterScience to arrange continued access to this content
• Access this journal at Wiley InterScience
• ingentaconnect is not responsible for the content or availability of external websites

Related content

• In this: publication
• By this: publisher
• In this Subject: Pathology
• By this author: Francis J Descamps ;  Erik Martens ;  Florence Ballaux ;  Karel Geboes ;  Ghislain Opdenakker

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers