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

GIMENO, ML; MALVICINI, M; PERONE, MJ; ATORRASAGASTI, C; ANDREONE, L; FIORE, E; MAZZOLINI, GD; ONORATO, A; GARCÍA, M; BAYO, J

Mar del Plata

Congreso; LXIII Reunión Anual de la SAIC; 2018

Sociedad Argentina de Investigación Clínica

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. SPARC is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal and non-parenchymal hepatic cells and pancreatic cells. Studies have identified that SPARC has the ability to inhibit adipogenesis and to promote insulin resistance; 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 mice (SPARC-/-) mice displayed an abnormal insulin-regulated glucose metabolism. SPARC-deleted mice presented an increased adipose tissue deposition and a severe hydrocarbon metabolism alteration in an age-dependent manner. In addition, the absence of SPARC worsens high-fat-diet-induced diabetes in mice. Interestingly, although SPARC-/- mice on high-fat diet were sensible to insulin they showed an impaired insulin secretion capacity. Of note is that the presence of GLUT2 glucose transporter in pancreatic islets from SPARC-/- mice was strongly reduced. This study provides the first evidence that deleted SPARC expression causes DBT in mice. Thus, SPARC deficient mice constitute a valuable model for future studies concerning obesity and its related metabolic complications.