Novel role for matricellular proteins in the regulation of islet ß cell survival: the effect of SPARC on survival, proliferation, and signaling.
J Biol Chem
; 289(44): 30614-30624, 2014 Oct 31.
Article
en En
| MEDLINE
| ID: mdl-25204658
ABSTRACT
Understanding the mechanisms regulating islet growth and survival is critical for developing novel approaches to increasing or sustaining ß 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 ß 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 ß 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 ß cells and primary mouse islets, and inhibits IGF-1-induced proliferation of INS-1 ß 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 ß cell growth.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Osteonectina
/
Supervivencia Celular
/
Proliferación Celular
/
Células Secretoras de Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido