Carob fruit extract-enriched meat improves pancreatic beta-cell dysfunction, hepatic insulin signaling and lipogenesis in late-stage type 2 diabetes mellitus model
2020
Macho-González, Adrián | López-Oliva, M Elvira | Merino, José J. | García-Fernández, Rosa A. | Garcimartín, Alba | Redondo-Castillejo, Rocío | Bastida, Sara | Sánchez-Muniz, Francisco J. | Benedí, Juana
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.
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