RT Journal Article T1 Carob fruit extract-enriched meat improves pancreatic beta-cell dysfunction, hepatic insulin signaling and lipogenesis in late-stage type 2 diabetes mellitus model A1 Macho González, Adrián A1 López-Oliva Muñoz, María Elvira A1 Merino Martín, José Joaquín A1 García Fernández, Rosa Ana A1 Garcimartín Álvarez, Alba A1 Bastida Codina, Sara A1 Redondo Castillejo, Rocío A1 Sánchez Muniz, Francisco José A1 Benedí González, Juana María AB The inclusion of functional bioactive compounds of dietary fiber in meat products has been demonstrated to exert a significant impact on human health. Carob fruit extract (CFE) is a dietary fiber rich in proanthocyanidins with known antioxidant, hypolipidemic and hypoglycemic effects. Consumption of CFE-enriched meat (CFE-RM) may provide interesting benefits in late-stage type 2 diabetes mellitus (T2DM). To explore the antidiabetic mechanisms of CFE-RM, we used a model of late-stage T2DM in Wistar rats fed a high-saturated-fat/high-cholesterol diet (Chol-diet) and injected streptozotocin plus nicotinamide (D group). The effects of CFE-RM were tested by incorporating it into the diet as preventive strategy (ED group) or curative treatment (DE group). CFE-RM had a positive effect on glycemia, enhancing hepatic insulin sensitivity and improving pancreatic β-cell regeneration in both ED and DE groups. Western blotting and immunohistochemistry suggested that CFE-RM increased levels of insulin receptor β and phosphatidylinositol-3-kinase, as well as the downstream target phospho-Akt (at Ser473). CFE-RM also up-regulated glucose transporter 2, which improves the insulin-mediated glucose uptake by the liver, and promoted phosphorylation of glycogen synthesis kinase-3βprotein (at ser9), consequently increasing the hepatic glycogen content. In addition, CFE-RM decreased fatty liver by suppressing de novo lipogenesis activation due to down-regulation of liver X receptor-α/β, sterol regulatory element binding protein-1c and carbohydrate-response element-binding protein transcription factors. Our findings suggest that the consumption of CFE-RM included in the diet as a functional food should be considered as a suitable nutritional strategy to prevent or manage late-stage T2DM. PB Elsevier SN 0955-2863 YR 2020 FD 2020-10 LK https://hdl.handle.net/20.500.14352/92352 UL https://hdl.handle.net/20.500.14352/92352 LA eng NO Macho-González A, López-Oliva ME, Merino JJ, García-Fernández RA, Garcimartín A, Redondo-Castillejo R, et al. Carob fruit extract-enriched meat improves pancreatic beta-cell dysfunction, hepatic insulin signaling and lipogenesis in late-stage type 2 diabetes mellitus model. The Journal of Nutritional Biochemistry 2020;84:108461. https://doi.org/10.1016/j.jnutbio.2020.108461. NO Ministerio de Educación, Cultura y Deporte (España) NO Banco Santander NO Universidad Complutense de Madrid DS Docta Complutense RD 7 abr 2025