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

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

Congreso; Reunión Conjunta de SAIC, SAI y SAFIS; 2018

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 demonstrated that SPARC inhibits adipogenesis and promotes insulin resistance; in addition, circulating SPARC levels were positively correlated with BMI 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 studied SPARC+/+ and SPARC-/- mice maintained on a normal low-fat (LF) or high fat (HF) diet. Animals in each group were euthanized after 12 or 20 weeks of WD or CD feeding. SPARC+/+ and SPARC-/- mice fed with CD were also studies at different time point since weaning (6 animals per group). We assessed glucose levels, glucose tolerance, insulin and c-peptide secretion.We show here that 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 (GLUT2) in islets of SPARC-/- mice was dramatically reduced. This 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.