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- Grunddal, K. V., et al.
(författare)
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Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats
- 2022
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65, s. 1018-1031
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Tidskriftsartikel (refereegranskat)abstract
- Aim/hypothesis Urocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved. Methods We studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis. Results In rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3's cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion. Conclusions/interpretation Our combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions.
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| 2. |
- Laursen, Martin F., et al.
(författare)
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Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut
- 2021
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6, s. 1367-1382
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Tidskriftsartikel (refereegranskat)abstract
- Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.
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| 4. |
- Shyam, Priyank, et al.
(författare)
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Sintering in seconds, elucidated by millisecond in situ diffraction
- 2023
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Ingår i: Applied Materials Today. - 2352-9407. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Materials, when sintered at high temperatures, undergo structural changes on multiple, hierarchical length scales but getting realtime information on these changes is difficult. To address this challenge, we developed a custom-built sample environment that allows us to investigate the structural evolution of materials during sintering using high-energy two-dimensional synchrotron X-ray diffraction (2D-XRD). Changes in the structure of SrFe12O19 ceramic magnet at multiple length scales were tracked in situ and modelled with millisecond time-resolution. In addition, we also demonstrated the ability to perform quantitative texture analysis from individual 2D-XRD images with a time resolution of 4 ms each. Owing to the high brightness X-ray source and advanced X-ray detectors, the evolution of crystallographic texture could be followed during sintering. This in situ approach can aid understanding of the synthesis–structure–property relationships in sintered materials, enabling the development of improved functional materials.
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