| 1. |
- Trabelsi, M. S., et al.
(författare)
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Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and the nuclear receptor FXR. BA sequestrants (BAS) complex bile acids in the intestinal lumen and decrease intestinal FXR activity. The BAS-BA complex also induces glucagon-like peptide-1 (GLP-1) production by L cells which potentiates beta-cell glucose-induced insulin secretion. Whether FXR is expressed in L cells and controls GLP-1 production is unknown. Here, we show that FXR activation in L cells decreases proglucagon expression by interfering with the glucose-responsive factor Carbohydrate-Responsive Element Binding Protein (ChREBP) and GLP-1 secretion by inhibiting glycolysis. In vivo, FXR deficiency increases GLP-1 gene expression and secretion in response to glucose hence improving glucose metabolism. Moreover, treatment of ob/ob mice with the BAS colesevelam increases intestinal proglucagon gene expression and improves glycaemia in a FXR-dependent manner. These findings identify the FXR/GLP-1 pathway as a new mechanism of BA control of glucose metabolism and a pharmacological target for type 2 diabetes.
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| 2. |
- Castillo, N.A., et al.
(författare)
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Identifying pathways of pharmaceutical exposure in a mesoconsumer marine fish
- 2024
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 477
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical uptake involves processes that vary across aquatic systems and biota. However, single studies examining multiple environmental compartments, microhabitats, biota, and exposure pathways in mesoconsumer fish are sparse. We investigated the pharmaceutical burden in bonefish (Albula vulpes), pathways of exposure, and estimated exposure to a human daily dose. To evaluate exposure pathways, the number and composition of pharmaceuticals across compartments and the bioconcentration in prey and bonefish were assessed. To evaluate bioaccumulation, we proposed the use of a field-derived bioaccumulation factor (fBAF), due to variability inherent to natural systems. Exposure to a human daily dose was based on bonefish daily energetic requirements and consumption rates using pharmaceutical concentrations in prey. Pharmaceutical number and concentration were highest in prey, followed by bonefish, water and sediment. Fifteen pharmaceuticals were detected in common among bonefish, prey, and water; all of which bioconcentrated in prey and bonefish, and four bioaccumulated in bonefish. The composition of detected pharmaceuticals was compartment specific, and prey were most similar to bonefish. Bonefish were exposed to a maximum of 1.2 % of a human daily dose via prey consumption. Results highlight the need for multicompartment assessments of exposure and consideration of prey along with water as a pathway of exposure.
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