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

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

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2019 vol. 133 p. 351 - 365

0143-5221

Obesity, metabolic syndrome and type 2 diabetes, three strongly interrelated diseases,are associated to increased morbidity and mortality worldwide. The pathogenesis ofobesity-associated disorders is still under study. SPARC is a matricellular glycoproteinexpressed in many cell types including adipocytes, parenchymal and non-parenchymalhepatic cells and pancreatic cells. Studies have demonstrated that SPARC inhibitsadipogenesis and promotes insulin resistance; in addition, circulating SPARC levelswere positively correlated with BMI in obese individuals. Therefore, SPARC is beingproposed as a key factor in the pathogenesis of obesity-associated disorders. The aim ofthis study is to elucidate the role of SPARC in glucose homeostasis. We show here thatSPARC null (SPARC-/-) mice displayed an abnormal insulin-regulated glucosemetabolism. SPARC-/- mice presented an increased adipose tissue deposition and aimpaired glucose homeostasis as animals aged. In addition, the absence of SPARCworsens high-fat diet-induced diabetes in mice. Interestingly, although SPARC-/- miceon high-fat diet were sensitive to insulin they showed an impaired insulin secretioncapacity. Of note, the expression of glucose transporter 2 (GLUT2) in islets of SPARC-/-mice was dramatically reduced. This study provides the first evidence that deletedSPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute avaluable model for studies concerning obesity and its related metabolic complications,including diabetes.