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- Chuang, Shu-Chun, et al.
(författare)
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Circulating Biomarkers of Tryptophan and the Kynurenine Pathway and Lung Cancer Risk
- 2014
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:3, s. 461-468
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Tidskriftsartikel (refereegranskat)abstract
- Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer andNutrition (EPIC) that included 893 incident lung cancer cases and 1,748matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: Tryptophan (P-trend = 2 Chi 10(-5)) and the kynurenine/ tryptophan ratio (KTR; P-trend 4 Chi 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th (vs. 1st)) were 0.52 [ 95% confidence interval (CI), 0.37-0.74] for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available fromprevious work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted P-trend 0.13) and KTR (P-trend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, P-trend -3 Chi 10(-5)) that was only marginally affected by adjusting for methionine. Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
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- Goedecke, J H, et al.
(författare)
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Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women
- 2015
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39:2, s. 303-311
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Tidskriftsartikel (refereegranskat)abstract
- Background: Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown.Objective: The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences.Methods: Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11β-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures.Results: Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women.Conclusions: In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.
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- Rask, Eva, 1958-, et al.
(författare)
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Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men
- 2001
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:9, s. 1640-1645
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake.RESEARCH DESIGN AND METHODS:From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured.RESULTS:Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response after the mixed meal was associated with insulin sensitivity (r = 0.54, P < 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P < 0.05). GLP-1 levels 15 min after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin responses.CONCLUSIONS:In insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.
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- Dahlqvist, Per, et al.
(författare)
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Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats
- 1999
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Ingår i: Neuroscience. - 1873-7544 .- 0306-4522. ; 93:2, s. 527-535
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Tidskriftsartikel (refereegranskat)abstract
- Housing rats in an enriched environment after focal brain ischemia improves functional outcome without changes in infarct volume, suggesting neuroplastic changes outside the lesion. In this study, permanent occlusion of the middle cerebral artery was followed by housing in an enriched or a standard environment. Nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression were determined by in situ hybridization two to 30 days after middle cerebral artery occlusion. Stroke induced a decrease in nerve growth factor-induced gene A messenger RNA expression in cortical areas outside the ischemic lesion and in the CA1 subregion of the hippocampus two to three days after ischemia. This decrease was more prolonged with environmental enrichment, lasting until 20 days. However, 30 days after focal cerebral ischemia, environmental enrichment increased nerve growth factor-induced gene A expression compared to standard housing. A reduction of hippocampal glucocorticoid receptor (type II) messenger RNA two to 12 days after stroke in standard housed rats was restored by environmental enrichment. These data suggest that improved functional outcome induced by environmental enrichment after middle cerebral artery occlusion is associated with dynamically altered expression of nerve growth factor-induced gene A messenger RNA in brain regions outside the ischemic lesion, and sustained levels of hippocampal glucocorticoid receptor messenger RNA expression.
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