| 151. |
- Rotter Sopasakis, Victoria, 1972, et al.
(författare)
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High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator
- 2004
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Ingår i: Obes Res. - 1071-7323. ; 12:3, s. 454-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the possibility that interleukin-6 (IL-6) can act as a paracrine regulator in adipose tissue by examining effects on adipogenic genes and measuring interstitial IL-6 concentrations in situ. RESEARCH METHODS AND PROCEDURES: Circulating and interstitial IL-6 concentrations in abdominal and femoral adipose tissue were measured using the calibrated microdialysis technique in 20 healthy male subjects. The effects of adipose cell enlargement on gene expression and IL-6 secretion were examined, as well as the effect of IL-6 in vitro on gene expression of adiponectin and other markers of adipocyte differentiation. RESULTS: The IL-6 concentration in the interstitial fluid was approximately 100-fold higher than that in plasma, suggesting that IL-6 may be a paracrine regulator of adipose tissue. This was further supported by the finding that adding IL-6 in vitro at similar concentrations down-regulated the expression of adiponectin, aP2, and PPARgamma-2 in cultured human adipose tissue. In addition, gene expression and release of IL-6, both in vivo and in vitro, correlated with adipose cell size. DISCUSSION: These data suggest that IL-6 may be a paracrine regulator of adipose tissue. Furthermore, increased adipose tissue production of IL-6 after hypertrophic enlargement of the adipose cells may detrimentally affect systemic insulin action by inducing adipose tissue dysfunction with impaired differentiation of the pre-adipocytes and/or adipocytes and lower adiponectin.
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| 152. |
- Rönn, Tina, et al.
(författare)
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Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:13, s. 3792-3813
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Tidskriftsartikel (refereegranskat)abstract
- Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed DNA methylation of ∼480,000 sites in human adipose tissue from 96 males and 94 females, and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1,050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of ageing in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2,825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with methylation of 711 sites, annotated to e.g. RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for metabolic diseases and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.
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| 153. |
- Sandqvist, Madelene, 1974, et al.
(författare)
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Decreased Permeability Surface Area for Glucose in Obese Women with Postprandial Hyperglycemia: No Effect of Phosphodiesterase-5 (PDE-5) Inhibition
- 2013
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 45:8, s. 556-560
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-mediated microvascular recruitment is recognized as a potential mechanism contributing to insulin resistance. In this study, we compared a marker of microvascular function, the permeability surface area for glucose (PSglu), and forearm glucose uptake after an OGTT in obese women with impaired glucose metabolism and healthy lean nondiabetic women, with the aim to characterize whether decreased permeability surface area for glucose or decreased glucose uptake may contribute to postprandial hyperglycemia in the obese group. In addition, we evaluated whether the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, in a randomized double blind placebo controlled design, might attenuate postprandial glucose levels in obese women. For these purposes, intramuscular microdialysis, blood sampling from arterial and venous blood of the forearm, and measurements of forearm blood flow were performed. The results showed an impaired permeability surface area for glucose (IAUC PSglu 31 +/- 13 vs. 124 +/- 31; p < 0.05) in obese when compared with lean participants, but no differences in forearm glucose uptake appeared between the groups. Furthermore, a single dose of tadalafil 10 mg showed no improvement of the permeability surface area for glucose, glucose uptake, or circulating glucose levels in obese participants. In conclusion, the postprandial PSglu response was impaired in obese women showing postprandial hyperglycemia, indicating a compromised microcirculation. However, we were unable to demonstrate any acute effect on either vascular function or glucose uptake of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil.
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| 154. |
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| 155. |
- Sandqvist, Madelene, 1974, et al.
(författare)
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Low adipocyte IRS-1 protein expression is associated with an increased arterial stiffness in non-diabetic males
- 2005
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 180:1, s. 119-25
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Low adipocyte IRS-1 protein expression is a biomarker for insulin resistance and early atherosclerosis. However, whether IRS-1 protein expression is related to systemic arterial stiffness, is unknown. METHODS AND RESULTS: Ten non-diabetic male subjects with low adipocyte IRS-1 protein expression (LIRS) were matched with 10 non-diabetic males with normal IRS-1 protein expression (NIRS). Augmentation index (AIx) and time for reflection of pulse wave (Tr) were studied with pulse wave analysis, both in the fasting state and during a euglycemic hyperinsulinemic clamp. The LIRS-group showed an increased fasting insulin concentration (fP-insulin 71+/-4 pmol/L versus 58+/-5 pmol/L; p=0.02 (mean+/-S.E.)), whereas glucose disposal rate during the clamp (8.7+/-0.8 mg/kg LBM/min versus 10.3+/-1.3 mg/kg LBM/min; n.s.) did not differ significantly. Blood pressure, lipid parameters, adiponectin, endothelin-1 and CRP concentrations were similar. However, in the basal state, AIx was increased (129+/-4% versus 116+/-2%; p<0.02) and Tr was decreased (150+/-3 ms versus 171+/-5 ms; p<0.01), suggesting stiffer vessels in the LIRS-group. The LIRS-group exhibited an attenuated AIx response to hyperinsulinemia compared to the NIRS-group. CONCLUSIONS: The data suggest that non-obese non-diabetic men with a low adipocyte IRS-1 protein expression have an increased systemic arterial stiffness.
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| 156. |
- Sandqvist, Madelene, 1974, et al.
(författare)
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Postprandial interstitial insulin concentrations in type 2 diabetes relatives
- 2006
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Ingår i: Eur J Clin Invest. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:6, s. 383-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.
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| 157. |
- Sandstedt, Mikael, 1990, et al.
(författare)
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Wide QRS-T angles are associated with markers of increased inflammatory activity independently of hypertension and diabetes.
- 2020
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Ingår i: Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. - : Wiley. - 1542-474X. ; 25:6
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Tidskriftsartikel (refereegranskat)abstract
- Wide QRS-T angles and inflammatory activity are markers of future cardiovascular events including sudden cardiac death (SCD). The association between wide QRS-T angles and inflammatory activation is however not fully understood.1,094 study participants of both sexes, 50-64years old, were included from a randomly selected population-based cohort as a part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot study. Serum samples were analyzed for markers of inflammation, cardiac wall stress/injury, and the metabolic syndrome. Wide QRS-T angles were defined using Frank vectorcardiography. Variables were analyzed through unsupervised principal component analysis (PCA) as well as Orthogonal Projections to Latent Structures (OPLS) modeling. In addition, a subset of study participants was analyzed in a post hoc matched group design.Wide QRS-T angles correlated positively with markers of inflammation, cardiac wall stress/injury, the metabolic syndrome, and male sex in both PCA and OPLS models. In the matched post hoc analysis, participants with wide QRS-T angles had significantly higher counts of white blood cells (WBC) and neutrophils in comparison with matched controls. WBC as well as the number of neutrophils, monocytes, basophils, eosinophils and levels of C-reactive protein, IL-1, IL-4, IL-6, TNF-α, and NT-pro-BNP were also significantly higher in comparison with healthy controls.Markers of inflammatory activation and cardiac injury/wall stress were significantly higher in the presence of wide QRS-T angles. These results corroborate an association between abnormal electrophysiological function and inflammatory activation and may have implications for the prediction of SCD.
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| 158. |
- Sjörs, Anna, et al.
(författare)
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Increased insulin secretion and decreased glucose concentrations, but not allostatic load, are associated with stress-related exhaustion in a clinical patient population
- 2013
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Ingår i: Stress-the International Journal on the Biology of Stress. - : Informa UK Limited. - 1025-3890 .- 1607-8888. ; 16:1, s. 24-33
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Tidskriftsartikel (refereegranskat)abstract
- Allostatic load (AL) has been shown to be a useful marker of physiological strain during chronic stress and burnout in non-clinical working populations. The usability of the AL index for a clinical population with severe stress-related exhaustion was tested in this study. Thirteen biomarkers assembled as an AL index were analysed using blood samples from 90 patients with stress-related exhaustion (43 men and 47 women, age 31-61 years) and 90 healthy controls (46 men and 44 women, age 25-56 years). The AL scores did not differ between patients and controls. For men, some indication of higher cardiovascular risk was seen in the patient group: male patients had higher body mass index and waist-hip ratio and a poorer blood lipid status than male controls. We found lower plasma glucose concentrations in both female and male patients than those in controls. The male patients also showed increased fasting serum insulin concentrations. Further analysis using homeostasis model assessment for insulin resistance and beta-cell function showed indications of insulin resistance in the patient group, particularly in the males, and an increased insulin secretion in both male and female patients. In conclusion, AL index does not seem to capture plausible physiological strain in patients diagnosed with stress-related exhaustion. The finding of lower plasma glucose concentrations, probably due to higher insulin secretion, in patients with severe stress-related exhaustion, needs to be further investigated, including mechanisms and the clinical relevance.
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| 159. |
- Sjöstrand, M, et al.
(författare)
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Repeated measurements of 11β-HSD-1 activity in subcutaneous adipose tissue from lean, abdominally obese, and type 2 diabetes subjects--no change following a mixed meal.
- 2010
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Ingår i: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 42:11, s. 798-802
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to measure 11β-HSD-1 activity in subcutaneous adipose tissue by an ex vivo method in three subgroups; lean, obese, and type 2 diabetes subjects, both in the fasting state and after a mixed meal and to determine the variability and reproducibility of this method. Eighteen subjects were investigated; 6 lean, 6 abdominally obese, and 6 type 2 diabetes subjects (BMI 22 ± 1, 30 ± 3 and 31 ± 3 kg/m², respectively). Needle biopsies were taken repeatedly and an index of 11β-HSD-1 activity was measured as percent conversion of (3)H-cortisone to (3)H-cortisol/100 mg tissue. For two separate biopsies taken in the fasting state on the same day, the within subjects CV was 16% and the between CV was 36% for 11β-HSD-1 activity for all subjects. For two biopsies taken in the fasting state at two different days, the total within subjects CV was 38% and the between subjects CV was 46%. Lean subjects had lower 11β-HSD-1 activity (4.8 ± 1.5% conversion of ³H-cortisone to ³H-cortisol/100 mg tissue) than both obese (14.4 ± 1.6% conversion, p<0.01) and type 2 diabetes subjects (11.7 ± 1.9% conversion, p<0.05) in the fasting state. There was no effect of a meal on 11β-HSD-1 activity in any of the three groups. The conclusions from this study are: 1) the variation coefficient for the ex vivo adipose tissue 11β-HSD-1 activity method was ∼25% for repeat measures within subjects; 2) food intake had no major impact on enzyme activity; and 3) 11β-HSD-1 activity in subcutaneous adipose tissue was significantly increased in obese subjects with or without T2DM compared to lean subjects without diabetes.
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| 160. |
- Smith, Ulf, 1943, et al.
(författare)
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Insulin signaling and action in fat cells: associations with insulin resistance and type 2 diabetes.
- 1999
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Ingår i: Annals of the New York Academy of Sciences. - 0077-8923. ; 892, s. 119-26
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Forskningsöversikt (refereegranskat)abstract
- Adipose tissue only accounts for a relatively small proportion (< 10%) of the peripheral glucose utilization in response to insulin. However, the fat cells may still play an important role in insulin resistance and Syndrome X through, for instance, its endocrine functions (production of leptin, TNF alpha, PAI-1, etc.) and involvement in lipid metabolism (FFA release and hydrolysis of triglycerides). The fat cells are also highly sensitive to insulin and may thus be used to elucidate molecular mechanisms for insulin resistance in man. Examinations of the intracellular signaling mechanisms for insulin in fat cells from individuals with Type 2 diabetes revealed markedly lower insulin-stimulated PI3-kinase activity. This was due to a pronounced reduction in the cellular expression of the docking protein, IRS 1, whereas expression of IRS 2 was normal. However, IRS 2-associated PI3-kinase activity was only approximately one-third of that found to be associated with IRS 1 in normal cells. Downstream activation and serine phosphorylation of PKB/Akt by insulin were also markedly reduced in Type 2 diabetes. Furthermore, the dose-response curve for this effect of insulin was similar to that for glucose transport in both normal and Type 2 diabetic cells. Thus, these data show that both PI3-kinase and PKB activation by insulin are markedly reduced in Type 2 diabetes. We also examined whether an attenuated activation of PI3-kinase by insulin can be seen in non-diabetic insulin-resistant states. Approximately 30% of healthy subjects with at least two first-degree relatives with Type 2 diabetes exhibited perturbations in IRS-1 expression and signaling. These individuals were characterized by insulin resistance as well as other markers of Syndrome X. Thus, impaired IRS-1 expression and downstream signaling events in fat cells in response to insulin are associated with insulin resistance and Syndrome X.
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