Search

Sodium-glucose cotransporter 1 (SGLT1) is the primary transporter for glucose absorption from digested nutrients in the gastrointestinal tract. Intestinal SGLT1 inhibition reduces post-prandial hyperglycemia and enhances the increase of plasma glucagon-like peptide-1 (GLP-1) levels. SGL5213 is a novel and potent intestinal SGLT1 inhibitor. This study characterizes the pharmacological profiles of SGL5213 in rodents. Orally administered SGL5213 was hardly absorbed and its distribution was restricted to the gastrointestinal lumen. SGL5213 significantly improved post-prandial hyperglycemia in streptozotocin (STZ)-induced diabetic rats at doses of 1 mg/kg or more. After the oral administration of starch, SGL5213 increased the amount of residual glucose in the small intestine at 1-3 h and in the cecum and colon at 3-9 h by inhibiting glucose absorption and allowing the unabsorbed glucose to be delivered into the lower-gastrointestinal tract. In the vehicle group, the plasma total GLP-1 (tGLP-1) and tGLP-2 levels increased at 15 min and the plasma total glucose-dependent insulinotropic polypeptide (tGIP) level increased at 1 h after meal loading. SGL5213 at doses of 0.1 mg/kg or more enabled the plasma levels of tGLP-1 and tGLP-2 to be retained for a period of 1-6 h, compared with the vehicle group. In contrast, SGL5213 at doses of 0.3 mg/kg or more suppressed the plasma tGIP elevation after meal loading. This study demonstrated for the first time that an intestinal SGLT1 inhibitor enhanced post-prandial plasma GLP-2 secretion. These results suggest that SGL5213 might exhibit a useful pharmacological efficacy through the physiological actions of GLP-1 and GLP-2., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6 J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 weeks. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40-60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cyclooxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 (GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between. The intestinal barrier function was assessed by lactulose-mannitol excretion in urine. Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay. In the inulin group, the urinary lactulose recovery was significantly lower than the other 2 groups. There were no significant differences in urinary mannitol levels between groups. Accordingly, the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups. The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups. The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2, suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)