. Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab 285: E106-E115, 2003. First published March 4, 2003 10.1152/ajpendo.00457.2002-Elevated levels of resistin have been proposed to cause insulin resistance and therefore may serve as a link between obesity and type 2 diabetes. However, its role in skeletal muscle metabolism is unknown. In this study, we examined the effect of resistin on insulinstimulated glucose uptake and the upstream insulin-signaling components in L6 rat skeletal muscle cells that were either incubated with recombinant resistin or stably transfected with a vector containing the myc-tagged mouse resistin gene. Transfected clones expressed intracellular resistin, which was released in the medium. Incubation with recombinant resistin resulted in a dose-dependent inhibition of insulin-stimulated 2-deoxyglucose (2-DG) uptake. The inhibitory effect of resistin on insulin-stimulated 2-DG uptake was not the result of impaired GLUT4 translocation to the plasma membrane. Furthermore, resistin did not alter the insulin receptor (IR) content and its phosphorylation, nor did it affect insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation, its association with the p85 subunit of phosphatidylinositol (PI) 3-kinase, or IRS-1-associated PI 3-kinase enzymatic activity. Insulin-stimulated phosphorylation of Akt/protein kinase B-␣, one of the downstream targets of PI 3-kinase and p38 MAPK phosphorylation, was also not affected by resistin. Expression of resistin also inhibited insulin-stimulated 2-DG uptake when compared with cells expressing the empty vector (L6Neo) without affecting GLUT4 translocation, GLUT1 content, and IRS-1/PI 3-kinase signaling. We conclude that resistin does not alter IR signaling but does affect insulin-stimulated glucose uptake, presumably by decreasing the intrinsic activity of cell surface glucose transporters. skeletal muscle; glucose transporter-4

PurposeThe microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV compositionMethodsTwenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively.ResultsThe proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level.ConclusionsWe suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.

Abstract:Rice koji, used early in the manufacturing process for many fermented foods, produces diverse metabolites and enzymes during fermentation. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-performance liquid chromatography linear trap quadrupole ion trap tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS), and multivariate analysis we generated the metabolite profiles of rice koji produced by fermentation with Aspergillus oryzae (RK_AO) or Bacillus amyloliquefaciens (RK_BA) for different durations. Two principal components of the metabolomic data distinguished the rice koji samples according to their fermenter species and fermentation time. Several enzymes secreted by the fermenter species, including α-amylase, protease, and β-glucosidase, were assayed to identify differences in expression levels. This approach revealed that carbohydrate metabolism, serine-derived amino acids, and fatty acids were associated with rice koji fermentation by A. oryzae, whereas aromatic and branched chain amino acids, flavonoids, and lysophospholipids were more typical in rice koji fermentation by B. amyloliquefaciens. Antioxidant activity was significantly higher for RK_BA than for RK_AO, as were the abundances of flavonoids, including tricin, tricin glycosides, apigenin glycosides, and chrysoeriol glycosides. In summary, we have used MS-based metabolomics and enzyme activity assays to evaluate the effects of using different microbial species and fermentation times on the nutritional profile of rice koji.

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To evaluate the pharmacokinetic and pharmacodynamic characteristics of YH1885, a novel proton pump inhibitor, a single-blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 46 healthy volunteers. The volunteers were randomly allocated to single dose groups of 60 mg, 100 mg, 150 mg, 200 mg, and 300 mg (6 subjects per dose, including 2 placebos) or to multiple-dose groups of 150 mg and 300 mg (once-daily dosing for 7 days; 8 subjects per dose, including 2 placebos). The multiple-dose study was conducted separately after the single-dose study. YH1885 was administered orally after overnight fasting. Serial blood samples, urine samples, and pharmacodynamic measurements were taken. Drug concentrations in plasma and urine were determined by liquid chromatography/mass spectrometry (LC/MS). Pharmacodynamic changes were evaluated by ambulatory intragastric pH monitoring and by serial measurements of serum gastrin concentrations. Assessments of safety and tolerability also were made. Plasma concentrations of YH1885 reached peak levels 1.3 to 2.5 hours after single-dose administration and then declined monoexponentially with a terminal half-life (t(1/2)) of 2.2 to 2.4 hours in dosage groups up to 200 mg in the single-dose study. YH1885 showed linear pharmacokinetic characteristics, and little accumulation occurred after multiple administrations. The parent drug was not detected in urine. Dose-related pharmacological effects were obvious for dose groups of 150 mg and higher in the single-dose study. The mean intragastric pH and the percentage of time at pH>4 were significantly increased. The onset of drug effect was rapid, and maximal effects were observed on the first day of administration during multiple dosing. Serum gastrin levels also showed rapid increases during dosing but with a weak dose-effect relationship. Neither serious nor dose-limiting adverse effects were observed. YH1885 was found to be safe and well tolerated and effectively inhibited acid secretion with dose-dependent increases in intragastric pH. The acid-suppressing efficacy of YH1885 needs to be further evaluated in patients with gastric acid-related diseases.

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The Korean traditional hot sauce gochujang has been reported to have biological activities. Different kinds of gochujang products were prepared based on combinations of a fungal rice koji with two kinds of bacterial soybean mejus. Diets that included gochujang products were fed to rats and anti-obesity effects were investigated. Gochujang products reduced body weight gains, epididymal fat weights, and triglyceride levels in the serum and the liver. Effects were exerted by the diet that included the non-fermented gochujang mixture, increased using a fungal rice koji, and further enhanced using a bacterial soybean meju. Dietary effects were apparently induced via inhibition of the lipogenic enzymes fatty acid synthase, malic enzyme, and lipoprotein lipase by gochujang products in epididymal adipose tissues, and inhibition of glucose-6-phosphate dehydrogenase in the liver. High levels of capsaicin and genistein in gochujang products are considered to contribute to anti-obesity effects.