Search

Purpose: Bile acids (BAs) have been shown to contribute to glucose and energy homeostasis. We have recently reported that miglitol, an alpha-glucosidase inhibitor, increases fecal BA excretion and ameliorate insulin resistance and obesity in mice. The aim of this study was to clarify the mechanisms by which miglitol affects BA metabolism. The expression of genes regulating BA metabolism, gut microbiome and short-chain fatty acids (SCFA) were examined. Procedures: NSY mice, representing an obese type 2 diabetic model, were fed with a high-fat diet with or without miglitol for 4 weeks. The expression of BA-related genes in the liver and the lower intestine were measured. Alterations in fecal microbiome, fecal SCFA along with plasma lipid levels were also evaluated. Major findings: Miglitol significantly increased fecal BA secretion and markedly upregulated the mRNA expression, protein levels and enzyme activity of hepatic cholesterol 7α-hydroxylase, a rate-limiting enzyme of BA synthesis. In the intestine, miglitol treatment significantly suppressed the mRNA expression of apical sodium-dependent bile acid transporter and ATP-binding cassette transporter G5 and G8. In fecal microbiome, the prevalence of prevotella was remarkably reduced and that of clostridium subcluster XIVa was increased by miglitol. Miglitol elevated formic and n-butyric acids along with total SCFA concentration in feces, while succinic acid was decreased. There was no change in plasma total cholesterol levels. Conclusions: Collectively, miglitol may affect BA metabolism via enhanced CYP7A1 activity resulting from at least in part the alterations in gut microbiome and SCFA production in obese diabetic mice. Keywords: Alpha-glucosidase inhibitors, Bile acids, Cholesterol 7α-hydroxylase, Gut microbiome, Short-chain fatty acids, Miglitol

The article previews the PostgreSQL open-source database management system from NTT Open Source Software Center.

Fluorescence behaviors of a triethylenetetramine bearing anthracene (AN) and benzophenone (BP) fragments at the respective ends, L1, have been studied in water, where effects of pH (H) and metal cations on the emission properties have been studied in detail. L1behaves as a fluorescent molecular logic gate driven by H(Input1) and metal cations (Input2) as input chemicals. The most notable feature of L1is that this molecule expresses the “either−or” switchable dual logic functions. Operation of L1with Cu2as Input2expresses the INHIBIT logic function, where a strong AN fluorescence appears only at pH 4 (with H) without Cu2Input1(1)-Input2(0). In contrast, operations of L1with all other metal cations as Input2express the TRANSFER logic function, where the presence of Hallows strong AN fluorescence regardless of whether the metal cation exists or not Input1(1)-Input2(0); Input1(1)-Input2(1). These emission switching behaviors of L1are driven by the difference in the coordination stability between L1and metal cations and the photoinduced intramolecular electron and energy transfer processes:  (i) a pH-induced electron transfer from unprotonated nitrogen atoms of the polyamine chain to the photoexcited AN ELT(N→AN); (ii) a pH- and metal coordination-induced electron transfer from the photoexcited AN to the ground-state BP ELT(AN→BP); and (iii) a Cu2coordination-induced energy transfer from the photoexcited AN to Cu2ENT(AN→Cu2). [ABSTRACT FROM AUTHOR]