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Flavonoids are dietary compounds with potential anti-diabetes activities. Many flavonoids have poor bioavailability and thus low circulating concentrations. Unabsorbed flavonoids are metabolized by the gut microbiota to smaller metabolites, which are more bioavailable than their precursors. The activities of these metabolites may be partly responsible for associations between flavonoids and health. However, these activities remain poorly understood. We investigated bioactivities of flavonoid microbial metabolites [hippuric acid (HA), homovanillic acid (HVA), and 5-phenylvaleric acid (5PVA)] in primary skeletal muscle and β-cells compared to a native flavonoid ([(−)-epicatechin, EC]. In muscle, EC was the most potent stimulator of glucose oxidation, while 5PVA and HA simulated glucose metabolism at 25 μM, and all compounds preserved mitochondrial function after insult. However, EC and the metabolites did not uncouple mitochonndrial respiration, with the exception of 5PVA at10 μM. In β-cells, all metabolites more potently enhanced glucose-stimulated insulin secretion (GSIS) compared to EC. Unlike EC, the metabolites appear to enhance GSIS without enhancing β-cell mitochondrial respiration or increasing expression of mitochondrial electron transport chain components, and with varying effects on β-cell insulin content. The present results demonstrate the activities of flavonoid microbial metabolites for preservation of β-cell function and glucose utilization. Additionally, our data suggest that metabolites and native compounds may act by distinct mechanisms, suggesting complementary and synergistic activities in vivo which warrant further investigation. This raises the intriguing prospect that bioavailability of native dietary flavonoids may not be as critical of a limiting factor to bioactivity as previously thought.

Edited by L aszl o NagyUnderstanding the molecular pathways that enhance b-cell proliferation, survival, and insulin secretion may be useful to improve treatments for diabetes. Nkx6.1 induces proliferation through the Nr4a nuclear receptors, and improves insulin secretion and survival through the peptide hormone VGF. Here we demonstrate that Nkx6.1-mediated upregulation of Nr4a1, Nr4a3, and VGF is dependent on c-Fos expression. c-Fos overexpression results in activation of Nkx6.1 responsive genes and increases b-cell proliferation, insulin secretion, and cellular survival. c-Fos knockdown impedes Nkx6.1-mediated b-cell proliferation and insulin secretion. These data demonstrate that c-Fos is critical for Nkx6.1-mediated expansion of functional b-cell mass.

Background:Recently, there has been mounting evidence suggesting the efficacy of steroid-eluting stents (SES) for management of chronic rhinosinusitis a er endoscopic sinus surgery (ESS). This meta-analysis serves to evaluate the efficacy of SES in improving postoperative outcomes a er ESS. Methods:A systematic literature search was performed of PubMed for articles published between 1985 and 2018. The outcome variables were reported at, on average, 30 days postintervention.Results: Seven of the 76 published studies, all of which were industry-sponsored, were included for a collective cohort of 444 SES and 444 control sinuses. In patients who received SES vs controls, collective odds ratios (ORs) for postoperative need for intervention, surgery, and oral steroid were 0.45 (95% confidence interval [CI], 0.33-0.62; p < 0.001), 0.30 (95% CI, 0.18-0.52; p < 0.001), and 0.58 (95% CI, 0.40-0.84; p = 0.004), respectively. In addition, collective ORs for frontal sinus ostia (FSO) patency, moderate-to-severe adhesion/scarring, and increase in polyp score were 2.53 (95% CI, 1.61-3.97; p < 0.001), 0.28 (95% CI, 0.13-0.59; p < 0.001), and 0.42 (95% CI, 0.25-0.74; p = 0.002), respectively. Collective mean differences for FSO/ethmoid inflammation and FSO diameter were −10.86 mm (p < 0.001) and +1.34 mm (p < 0.001), respectively. Conclusion:Aggregate evidence suggests that SES can improve ESS outcomes by reducing rates of postoperative intervention and recurrent polyposis and inflammation, while promoting FSO patency. All included and analyzed studies were industry-sponsored and ruling-out publication bias was not possible. Future independent and nonsponsored studies to further evaluate SES's long-term efficacy are warranted. C 2019 ARS-AAOA, LLC.

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