| 1. |
- Hansen, Lea B.S., et al.
(författare)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 2. |
- Adlercreutz, Emma, et al.
(författare)
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A gluten free diet lowers NKG2D and ligand expression in BALB/c and NOD mice.
- 2014
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 177:2, s. 391-403
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between diet and immune-parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal upregulation of the activating receptor NKG2D(CD314) and its ligands is a hallmark of celiac disease (CD). However, the direct effect of gluten on NKG2D expression is not known. We studied, by FACS (lymphoid tissues) and RT-qPCR (intestine and pancreatic islets), if a gluten-free diet from 4 weeks (GF diet) or a gluten-free diet introduced in breeding pairs (SGF diet), induces changes in NKG2D expression on NK-cells DX5(+) (CD49b) and CD8(+) T-cells, as well as in intestinal and islet levels of NKG2D and ligands in BALB/c and NOD mice. Gluten-free NOD mice had lower insulitis (p<0.0001). Gluten-free NOD mice had reduced expression of NKG2D on DX5(+) NK-cells in spleen and auricular lymph nodes (p<0.05) and on CD8(+) T-cells in pancreas associated lymph nodes (p=0.04). Moreover, the level of CD71 on DX5(+) NK-cells and CD8(+) T-cells (p<0.005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (p<0.05). Differences in intestinal mRNA expression were found in mice of 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data shows that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.
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| 3. |
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| 4. |
- Blomqvist, Maria K., 1975, et al.
(författare)
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Sulfatide is associated with insulin granules and located to microdomains of a cultured beta cell line
- 2002
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Ingår i: Glycoconj J. - 0282-0080. ; 19:6, s. 403-13
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies using pancreas from various mammals and freshly isolated islets from rat pancreas have provided evidence supporting possible involvement of the glycosphingolipid sulfatide in insulin processing and secretion. In this study, sulfatide expression and metabolism in the beta cell line RINr1046-38 (RIN-38), commonly used as a model for beta cell functional studies, were investigated and compared with previous findings from freshly isolated islets. RIN-38 cells expressed similar amounts (2.7 +/- 1.1 nmol/mg protein, n = 19) of sulfatide as isolated rat islets and also followed the same metabolic pathway, mainly through recycling. Moreover, in agreement with findings in isolated islets, the major species of sulfatide isolated from RIN-38 cells contained C16:0 and C24:0 fatty acids. By applying subcellular isolations and electron microscopy and immunocytochemistry techniques, sulfatide was shown to be located to the secretory granules, the plasma membrane and enriched in detergent insoluble microdomains. In the electron microscopy studies, Sulph I staining was also associated with mitochondria and villi structures. In conclusion, RIN-38 cells might be an appropriate model, as a complement to isolated islets where the amount of material often limits the experiments, to further explore the role of sulfatide in insulin secretion and signal transduction of beta cells.
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| 5. |
- Blomqvist, Maria K., 1975, et al.
(författare)
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Uptake of the glycosphingolipid sulfatide in the gastrointestinal tract and pancreas in vivo and in isolated islets of Langerhans.
- 2006
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Ingår i: Lipids Health Dis. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The glycosphingolipid sulfatide has previously been found in several mammalian tissues, but information on the uptake of exogenously administered sulfatide in different organs in vivo is limited. In pancreatic beta cells, sulfatide has been shown to be involved in insulin processing and secretion in vitro. In this study, we examined the uptake of exogenously administered sulfatide and its distribution to the pancreatic beta cells. This might encourage future studies of the function(s) of sulfatide in beta cell physiology in vivo. Radioactive sulfatide was given orally to mice whereafter the uptake of sulfatide in the gastrointestinal tract and subsequent delivery to the pancreas was examined. Sulfatide uptake in pancreas was also studied in vivo by i.p. administration of radioactive sulfatide in mice, and in vitro in isolated rat islets. Isolated tissue/islets were analysed by scintillation counting, autoradiography and thin-layer chromatography-ELISA. RESULTS: Sulfatide was taken up in the gastrointestinal tract for degradation or further transport to other organs. A selective uptake of short chain and/or hydroxylated sulfatide fatty acid isoforms was observed in the small intestine. Exogenously administered sulfatide was found in pancreas after i.p, but not after oral administration. The in vitro studies in isolated rat islets support that sulfatide, independently of its fatty acid length, is endocytosed and metabolised by pancreatic islets. CONCLUSION: Our study supports a selective uptake and/or preservation of sulfatide in the gastrointestinal tract after oral administration and with emphasises on pancreatic sulfatide uptake, i.p. administration results in sulfatide at relevant location. PMID: 17044925 [PubMed - indexed for MEDLINE]
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| 6. |
- Braun, Matthias, et al.
(författare)
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GABAB-receptor activation inhibits exocytosis in rat pancreatic {beta}-cells by G-protein-dependent activation of calcineurin.
- 2004
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Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 559:2, s. 397-409
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the regulation of hormone secretion from rat pancreatic islets by the GABAB receptors (GABABRs). Inclusion of the specific GABABR antagonist CGP 55845 in the extracellular medium increased glucose-stimulated insulin secretion 1.6-fold but did not affect the release of glucagon and somatostatin. Conversely, addition of the GABABR agonist baclofen inhibited glucose-stimulated insulin secretion by ∼60%. Using RT-PCR, transcription of GABABR1a-c,f and GABABR2 subunits was detected in β-cells. Measurements of membrane currents and cell capacitance were applied to single β-cells to investigate the mechanisms by which GABABR activation inhibits insulin secretion. In perforated-patch measurements, baclofen inhibited exocytosis elicited by 500-ms voltage-clamp depolarizations to 0 mV by ≤ 80% and voltage-gated Ca2+ entry by only ∼30%. Both effects were concentration-dependent with IC50 values of ∼2 μm. The inhibitory action of baclofen was abolished in the presence of CGP 55845. The ability of baclofen to suppress exocytosis was prevented by pre-treatment with pertussis toxin and by inclusion of GDPβS in the intracellular medium, and became irreversible in the presence of GTPγS as expected for a process involving inhibitory G-proteins (Gi/o-proteins). The inhibitory effect of baclofen resulted from activation of the serine/threonine protein phosphatase calcineurin and pre-treatment with cyclosporin A or intracellular application of calcineurin autoinhibitory peptide abolished the effect. Addition of baclofen had no effect on [Ca2+]i and electrical activity in glucose-stimulated β-cells. These data indicate that GABA released from β-cells functions as an autocrine inhibitor of insulin secretion in pancreatic islets and that the effect is principally due to direct suppression of exocytosis.
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| 7. |
- Buschard, Karsten, et al.
(författare)
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C16:0 sulfatide inhibits insulin secretion in rat beta-cells by reducing the sensitivity of KATP channels to ATP inhibition
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:10, s. 2826-34
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Tidskriftsartikel (refereegranskat)abstract
- Sulfatide (3'-sulfo-beta-galactosyl ceramide) is a glycosphingolipid present in mammalians in various fatty acid isoforms of which the saturated 16 carbon-atom length (C16:0) is more abundant in pancreatic islets than in neural tissue, where long-chain sulfatide isoforms dominate. We previously reported that sulfatide isolated from pig brain inhibits glucose-induced insulin secretion by activation of ATP-sensitive K+ channels (K(ATP) channels). Here, we show that C16:0 sulfatide is the active isoform. It inhibits glucose-stimulated insulin secretion by reducing the sensitivity of the K(ATP) channels to ATP. (The half-maximal inhibitory concentration is 10.3 and 36.7 micromol/l in the absence and presence of C16:0 sulfatide, respectively.) C16:0 sulfatide increased whole-cell K(ATP) currents at intermediate glucose levels and reduced the ability of glucose to induce membrane depolarization, reduced electrical activity, and increased the cytoplasmic free Ca2+ concentration. Recordings of cell capacitance revealed that C16:0 sulfatide increased Ca2+-induced exocytosis by 215%. This correlated with a stimulation of insulin secretion by C16:0 sulfatide in intact rat islets exposed to diazoxide and high K+. C24:0 sulfatide or the sulfatide precursor, beta-galactosyl ceramide, did not affect any of the measured parameters. C16:0 sulfatide did not modulate glucagon secretion from intact rat islets. In betaTC3 cells, sulfatide was expressed (mean [+/-SD] 0.30 +/- 0.04 pmol/microg protein), and C16:0 sulfatide was found to be the dominant isoform. No expression of sulfatide was detected in alphaTC1-9 cells. We conclude that a major mechanism by which the predominant sulfatide isoform in beta-cells, C16:0 sulfatide, inhibits glucose-induced insulin secretion is by reducing the K(ATP) channel sensitivity to the ATP block.
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| 8. |
- Buschard, Karsten, et al.
(författare)
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Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
- 2005
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
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| 9. |
- Buschard, Karsten, et al.
(författare)
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Sulfatide and Longevity
- 2022
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X. ; 77:9, s. 1715-1716
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Cardwell, Chris R, et al.
(författare)
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Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies
- 2011
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Ingår i: INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. - : OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND. - 0300-5771 .- 1464-3685. ; 40:2, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I-2 = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children andlt; 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I-2 = 23%). Conclusion Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged andlt; 5 years. This finding could reflect increased exposure to infections in early life in later born children.
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