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Matrix Metalloproteinase-9 Is Essential for Physiological Beta Cell Function and Islet Vascularization in Adult Mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2015 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 185, no 4, 1094-1103 p.Article in journal (Refereed) Published
Abstract [en]

The availability of paracrine factors in the islets of Langerhans, and the constitution of the beta cell basement membrane can both be affected by proteolytic enzymes. This study aimed to investigate the effects of the extraceaular matrix-degrading enzyme gelatinase B/matrix metalloproteinase-9 (Mmp-9) on islet function in mice. Islet function of Mmp9-deficient (Mmp9(-/-)) mice and their wild-type Littermates was evaluated both in vivo and in vitro. The pancreata of Mmp9(-/-) mice did not differ from wild type in islet mass or distribution. However, Mmp9(-/-) mice had an impaired response to a glucose toad in vivo, with lower serum insulin levels. The glucose-stimulated insulin secretion was reduced also in vitro in isolated Mmp9(-/-) islets. The vascular density of Mmp9(-/-) islets was lower, and the capillaries had fewer fenestrations, whereas the islet blood flow was threefold higher. These alterations could partly be explained by compensatory changes in the expression of matrix-related proteins. This in-depth investigation of the effects of the loss of MMP9(-/-) function on pancreatic islets uncovers a deteriorated beta cell function that is primarily due to a shift in the beta cell phenotype, but also due to islet vascular aberrations. This likely reflects the importance of a normal islet matrix turnover exerted by MMP-9, and concomitant release of paracrine factors sequestered on the matrix.

Place, publisher, year, edition, pages
2015. Vol. 185, no 4, 1094-1103 p.
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Endocrinology and Diabetes
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URN: urn:nbn:se:uu:diva-251972DOI: 10.1016/j.ajpath.2014.12.009ISI: 000351787600019PubMedID: 25665793OAI: oai:DiVA.org:uu-251972DiVA: diva2:812326
Available from: 2015-05-18 Created: 2015-04-28 Last updated: 2017-12-04Bibliographically approved

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Christoffersson, GustafWaldén, TomasSandberg, MonicaCarlsson, Per-OlaPhillipson, Mia

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Integrative PhysiologyDepartment of Medical Cell Biology
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