info:eu-repo/semantics/article
SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice
Fecha
2019-01Registro en:
Atorrasagasti, María Catalina; Onorato, Agostina Mariana; Gimeno, Maria Laura; Andreone, Luz; García, Mariana Gabriela; et al.; SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice; Portland Press; Clinical Science; 133; 2; 1-2019; 351-365
0143-5221
CONICET Digital
CONICET
Autor
Atorrasagasti, María Catalina
Onorato, Agostina Mariana
Gimeno, Maria Laura
Andreone, Luz
García, Mariana Gabriela
Malvicini, Mariana
Fiore, Esteban Juan
Bayo Fina, Juan Miguel
Perone, Marcelo Javier
Mazzolini Rizzo, Guillermo Daniel
Resumen
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.