Increased Hypothalamic Anti-Inflammatory Mediators in Non-Diabetic Insulin Receptor Substrate 2-Deficient Mice

Cells

Ángela M. Valverde¹  Diana Grajales¹  Vítor Ferreira¹  Laura M. Frago²  Sandra Canelles²  Santiago Guerra-Cantera²  Vicente Barrios²  Ana Campillo-Calatayud²  Óscar Yanes³  María Vinaixa³  África González-Murillo⁴  Manuel Ramírez-Orellana⁴ 

[1]CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, E-28029 Madrid, Spain

[2]Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, Spain

[3]Metabolomics Platform, IISPV, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili, E-43002 Tarragona, Spain

[4]Unidad de Terapias Avanzadas, Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, E-28009 Madrid, Spain

关键词: diabetes;    hypothalamus;    inflammation;    IRS2^−/− mice;    PUFA;   

DOI  :  10.3390/cells10082085

来源: DOAJ

【 摘 要 】

Insulin receptor substrate (IRS) 2 is a key mediator of insulin signaling and IRS-2 knockout (IRS2^−/−) mice are a preclinical model to study the development of diabetes, as they develop peripheral insulin resistance and beta-cell failure. The differential inflammatory profile and insulin signaling in the hypothalamus of non-diabetic (ND) and diabetic (D) IRS2^−/− mice might be implicated in the onset of diabetes. Because the lipid profile is related to changes in inflammation and insulin sensitivity, we analyzed whether ND IRS2^−/− mice presented a different hypothalamic fatty acid metabolism and lipid pattern than D IRS2^−/− mice and the relationship with inflammation and markers of insulin sensitivity. ND IRS2^−/− mice showed elevated hypothalamic anti-inflammatory cytokines, while D IRS2^−/− mice displayed a proinflammatory profile. The increased activity of enzymes related to the pentose-phosphate route and lipid anabolism and elevated polyunsaturated fatty acid levels were found in the hypothalamus of ND IRS2^−/− mice. Conversely, D IRS2^−/− mice have no changes in fatty acid composition, but hypothalamic energy balance and markers related to anti-inflammatory and insulin-sensitizing properties were reduced. The data suggest that the concurrence of an anti-inflammatory profile, increased insulin sensitivity and polyunsaturated fatty acids content in the hypothalamus may slow down or delay the onset of diabetes.

【 授权许可】

Unknown