Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR

Impact of culture media glucose levels on the intestinal uptake of organic cations

There are several data concerning transporters expression and/or regulation in cell lines maintained in different conditions, such as medium glucose concentration. This work aimed to evaluate the influence of two different extracellular glucose concentrations, commonly used in culture media, on the intestinal absorption of organic cations. Thus, the effect of 5.5 mM glucose and 25 mM glucose (HG) in culture media, was studied on [3H]-MPP+ (1-methyl-4-phenylpyridinium iodide) uptake in Caco-2 cells. Expression of human organic cation transporter type 1 (hOCT1) and human organic cation transporter type 3 (hOCT3) was investigated in cells cultured at both glucose concentrations. [3H]-MPP+ uptake, as well as its affinity for the transporter, were significantly decreased in HG cells. Moreover, hOCT3 mRNA levels were reduced in HG cells. Functional confirmation of this result was made using hOCT3 inhibitors. In conclusion, maintenance of Caco-2 cells (commonly used in several in vitro studies on membrane transport) in HG conditions affects organic cation transport at the intestinal level. Hence, results obtained in these conditions must be analysed with great care, since extracellular glucose levels may originate changes in organic cation nutrient and drug bioavailability

The Influence of Some Nonsteroidal Anti-inflammatory Drugs on Metabolic Enzymes of Aldose Reductase, Sorbitol Dehydrogenase, and α-Glycosidase: a Perspective for Metabolic Disorders

Pain, as a sensible alarm signal of living organisms to avoid tissue damage, is a common and debilitating consequence of a lot of disorders and diseases. The management of chronic pain is particularly challenging. For pain treatment, many analgesic drugs are used for their therapeutic effects. In this study, some nonsteroidal anti-inflammatory drugs including etofenamate, meloxicam, diclofenac, and tenoxicam were tested against α-glycosidase from Saccharomyces cerevisiae, sorbitol dehydrogenase (SDH), and aldose reductase (AR) enzymes from sheep liver. Nonsteroidal anti-inflammatory drugs demonstrated useful inhibition properties against α-glycosidase, AR, and SDH enzymes. Ki values were found in the range of 11.93 ± 3.77–364.88 ± 40.01 μM for α-glycosidase, 3.36 ± 1.08μM–17.68 ± 3.39 mM for AR, and 1.68 ± 0.02 μM–30.98 ± 14.31 mM for SDH. They can be selective drugs as antidiabetic agents, because of their inhibitory properties against SDH, α-glycosidase, and AR enzymes. © 2019, Springer Science+Business Media, LLC, part of Springer Nature