Novel role for matricellular proteins in the regulation of islet [beta] cell survival: the effect of SPARC on survival, proliferation and signalling

Ryall, Claire, Viloria, Katrina, Lhaf, Fadel, Walker, Tony, King, Aileen, Jones, Peter, Mackintosh, David, Mcniece, Rosemary, Kocher, Hemant, Flodstrom-Tullberg, Malin, Edling, Charlotte and Hill, Natasha (2014) Novel role for matricellular proteins in the regulation of islet [beta] cell survival: the effect of SPARC on survival, proliferation and signalling. The Journal of Biological Chemistry, 289, pp. 30614-30624. ISSN (print) 0021-9258

Full text available as:
[img] Text
J. Biol. Chem.-2014-Ryall-jbc.M114.573980.pdf - Published Version
Restricted to Repository staff only

Download (5MB)

Abstract

Understanding the mechanisms regulating islet growth and survival is critical for developing novel approaches to increasing or sustaining β cell mass in both type 1 and type 2 diabetes patients. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that is important for the regulation of cell growth and adhesion. Increased SPARC can be detected in the serum of type 2 diabetes patients. The aim of this study was to investigate the role of SPARC in the regulation of β cell growth and survival. We show using immunohistochemistry that SPARC is expressed by stromal cells within islets and can be detected in primary mouse islets by western blot. SPARC is secreted at high levels by pancreatic stellate cells and is regulated by metabolic parameters in these cells, but SPARC expression was not detectable in β cells. In islets, SPARC expression is highest in young mice, and is also elevated in the islets of non-obese diabetic (NOD) mice compared to controls. Purified SPARC inhibits growth factor-induced signalling in both INS-1 β cells and primary mouse islets, and inhibits IGF-1-induced proliferation of INS-1 β cells. Similarly, exogenous SPARC prevents IGF-1-induced survival of primary mouse islet cells. This study identifies the stromal-derived matricellular protein SPARC as a novel regulator of islet survival and β cell growth.

Item Type: Article
Uncontrolled Keywords: Cell Growth, Diabetes, Extracellular Matrix Protein, Growth Factor, Islet, Regeneration, Signaling, Stromal Cell
Research Area: Allied health professions and studies
Biological sciences
Pharmacy
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing > School of Life Sciences
Related URLs:
Depositing User: Natasha Hill
Date Deposited: 01 Sep 2015 09:53
Last Modified: 11 Sep 2015 15:33
URI: http://eprints.kingston.ac.uk/id/eprint/30429

Actions (Repository Editors)

Item Control Page Item Control Page