SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice

Author:

Atorrasagasti Catalina1,Onorato Agostina1,Gimeno María L.2,Andreone Luz2,Garcia Mariana1,Malvicini Mariana1,Fiore Esteban1,Bayo Juan1,Perone Marcelo J.2,Mazzolini Guillermo D.1ORCID

Affiliation:

1. Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, CONICET- Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina

2. Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET - Partner Institute of the Max Planck Society, Buenos Aires, Argentina

Abstract

Abstract Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal, and non-parenchymal hepatic cells and pancreatic cells. Studies have demonstrated that SPARC inhibits adipogenesis and promotes insulin resistance; in addition, circulating SPARC levels were positively correlated with body mass index in obese individuals. Therefore, SPARC is being proposed as a key factor in the pathogenesis of obesity-associated disorders. The aim of this study is to elucidate the role of SPARC in glucose homeostasis. We show here that SPARC null (SPARC−/−) mice displayed an abnormal insulin-regulated glucose metabolism. SPARC−/− mice presented an increased adipose tissue deposition and an impaired glucose homeostasis as animals aged. In addition, the absence of SPARC worsens high-fat diet-induced diabetes in mice. Interestingly, although SPARC−/− mice on high-fat diet were sensitive to insulin they showed an impaired insulin secretion capacity. Of note, the expression of glucose transporter 2 in islets of SPARC−/− mice was dramatically reduced. The present study provides the first evidence that deleted SPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute a valuable model for studies concerning obesity and its related metabolic complications, including diabetes.

Publisher

Portland Press Ltd.

Subject

General Medicine

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