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 with controls. Purified SPARC inhibits growth factor-induced signaling 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.
Highlights
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that is increased in type 2 diabetes patients
SPARC is expressed by stromal cells within islets and inhibits growth factor responses and islet 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
Summary
SPARC is a matricellular protein that is increased in type 2 diabetes patients. Results: SPARC is expressed by stromal cells within islets and inhibits growth factor responses and islet survival. Conclusion: The matricellular protein SPARC is a novel regulator of islet survival. Significance: The regulation of stromal-derived matricellular proteins represents a novel approach to promoting islet growth or survival. Increased SPARC can be detected in the serum of type 2 diabetes patients. We show using immunohistochemistry that SPARC is expressed by stromal cells within islets and can be detected in primary mouse islets by Western blot. Purified SPARC inhibits growth factor-induced signaling in both INS-1  cells and primary mouse islets, and inhibits IGF-1-induced proliferation of INS-1  cells. This study identifies the stromal-derived matricellular protein SPARC as a novel regulator of islet survival and  cell growth
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