RESUMEN
The mucosal surface of gastrointestinal tract is lined with epithelial cells that establish an effective barrier between the lumen and internal environment through intercellular junctions, preventing the passage of potentially harmful substances. The "intestinal barrier function" consist of a defensive system that prevent the passage of antigens, toxins, and microbial products, while maintains the correct development of the epithelial barrier, the immune system and the acquisition of tolerance toward dietary antigens and intestinal microbiota. Intestinal morphology changes subsequent to nutritional variations, stress, aging or diseases, which can also affect the composition of the microbiota, altering the homeostasis of the intestine. A growing body of evidence suggests that alterations in intestinal barrier function favor the development of exaggerated immune responses, leading to metabolic endotoxemia, which seems to be the origin of many chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). Although the mechanisms are still unknown, the interaction between dietary patterns, gut microbiota, intestinal mucosa, and metabolic inflammation seems to be a key factor for the development of T2DM, among other diseases. This chapter details the different techniques that allow evaluating the morphological and molecular alterations that lead of the intestinal barrier dysfunction in a T2DM experimental model. To induce both diabetic metabolic disturbances and gut barrier disruption, Wistar rats were fed a high-saturated fat and high-cholesterol diet and received a single dose of streptozotocin/nicotinamide. This animal model may contribute to clarify the understanding of the role of intestinal barrier dysfunction on the late-stage T2DM etiology.
Asunto(s)
Diabetes Mellitus Tipo 2 , Ratas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Estreptozocina/metabolismo , Niacinamida/farmacología , Niacinamida/metabolismo , Ratas Wistar , Mucosa Intestinal/metabolismo , Colesterol/metabolismoRESUMEN
Epidemiological and experimental studies have suggested that dietary fiber and proanthocyanidins play an important role on gut microbiota (GM), colonic integrity and body health. Type 2 Diabetes Mellitus (T2DM) is a prevalent disease in which the modifications in the GM and colonic markers stand out. This manuscript hypothesizes the consumption of functional meat enriched in carob fruit extract [CFE; CFE-restructured meat (RM)] ameliorates the dysbiosis and colonic barrier integrity loss in a late-stage T2DM rat model induced by the conjoint action of a high-saturated-fat/high-cholesterol diet (Chol-diet) and a low dose of streptozotocin (STZ) plus a nicotinamide (NAD) injection. Three groups of eight rats were used: (1) D group, a T2DM control group, fed the Chol-diet; (2) ED group, a T2DM preventive strategy group fed the CFE-Chol-diet since the beginning of the study; and (3) DE group, a T2DM curative treatment group, fed the CFE-Chol-diet once the diabetic state was confirmed. The study lasted 8 weeks. Amount and variety of GM, feces short-chain-fatty acids (SCFAs), colonic morphology [crypt depth and density, goblet cells, proliferating cell nuclear antigen (PCNA) and transferase dUTP nick end labelling (TUNEL) indexes] and tight junctions were evaluated. A global colonic index combining 17 markers (GCindex) was calculated. ED rats displayed higher levels of GM richness, SCFAs production, crypt depth, and goblet cells than the D group. DE group showed lower Enterobacteriaceae abundance and greater TUNEL index and occludin expression in the distal colon than D counterpart. GCindex differentiated the colonic health status of the experimental groups in the order (ED > DE > D; P < 0.001) as a 17-51 range-quotation, ED, DE, and D groups displayed the values 43, 32.5, and 27, respectively. Thus, CFE-RM used as a T2DM preventive therapy could induce higher GM richness, more adequate SCFAs production, and better colonic barrier integrity. Furthermore, CFE-RM used with curative purposes induced more modest changes and mainly at the distal colonic mucosa. Further studies are needed to confirm this study's results, to ascertain the benefits of consuming proanthocyanidins-rich fiber during different T2DM stages.
Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animales , Colon , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/prevención & control , Frutas , Galactanos , Mananos , Carne , Gomas de Plantas , RatasRESUMEN
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 ß-cell regeneration in both ED and DE groups. Western blotting and immunohistochemistry suggested that CFE-RM increased levels of insulin receptor ß 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-3ßprotein (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/ß, 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.