| 1. |
- Plomgaard, P., et al.
(författare)
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Apolipoprotein M predicts pre-beta-HDL formation: studies in type 2 diabetic and nondiabetic subjects
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:3, s. 258-267
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Studies in mice suggest that plasma apoM is lowered in hyperinsulinaemic diabetes and that apoM stimulates formation of pre-beta-HDL. Pre-beta-HDL is an acceptor of cellular cholesterol and may be critical for reverse cholesterol transport. Herein, we examined whether patients with type 2 diabetes have reduced plasma apoM and whether apoM is associated with pre-beta-HDL formation and cellular cholesterol efflux. Design. In 78 patients with type 2 diabetes and 89 control subjects, we measured plasma apoM with ELISA, pre-beta-HDL and pre-beta-HDL formation, phospholipid transfer protein (PLTP) activity and the ability of plasma to promote cholesterol efflux from cultured fibroblasts. Results. ApoM was similar to 9% lower in patients with type 2 diabetes compared to controls (0.025 +/- 0.006 vs. 0.027 +/- 0.007 g L-1, P = 0.01). The difference in apoM was largely attributable to diabetes-associated obesity. ApoM was positively related to both HDL (r = 0.16; P = 0.04) and LDL cholesterol (r = 0.28; P = 0.0003). Pre-beta-HDL and pre-beta-HDL formation were not different between diabetic and control subjects. ApoM predicted pre-beta-HDL (r = 0.16; P = 0.04) and pre-beta-HDL formation (r = 0.19; P = 0.02), even independently of positive relationships with apoA-I, HDL-cholesterol and PLTP activity. Cellular cholesterol efflux to plasma was positively related to pre-beta-HDL and PLTP activity but not significantly to apoM. Conclusions. Plasma apoM is modestly reduced in type 2 diabetes. Pre-beta-HDL and pre-beta-HDL formation are positively associated with apoM, supporting the hypothesis that apoM plays a role in HDL remodelling in humans. Lower apoM may provide a mechanism to explain why pre-beta-HDL formation is not increased in type 2 diabetes despite elevated PLTP activity.
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| 2. |
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| 3. |
- Dullaart, Robin P. F., et al.
(författare)
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Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness
- 2009
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 406:1-2, s. 129-133
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Tidskriftsartikel (refereegranskat)abstract
- Background: Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (MetS) subjects, and determined whether intima media thickness (IMT) is associated with apoM. Methods: In 19 non-diabetic subjects with and 60 non-diabetic subjects without MetS (NCEP, ATP III criteria), the relationships of plasma apoM with obesity, glucose, insulin, lipids and adipokines, as well as with IMT were determined. Results: Plasma apoM was on average 15% lower in subjects with MetS compared to subjects without MetS (p=0.036). ApoM correlated inversely with body mass index and waist circumference (p<0.001), and positively with total cholesterol, LDL cholesterol and apoA-I (p<0.05). ApoM was not significantly correlated with glucose, insulin, leptin, adiponectin or resistin (p>0.20). Age- and sex adjusted IMT was lower in subjects with MetS (p<0.05), but was unrelated to apoM (p=0.68). In a multiple linear regression model that included the presence of both MetS and apoM, IMT was only related to MetS (p=0.05). Conclusions: Plasma apoM is reduced in MetS. In this study, apoM did not predict subclinical atherosclerosis. (C) 2009 Elsevier B.V. All rights reserved.
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| 4. |
- Gejl, K. D., et al.
(författare)
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Repeated high-intensity exercise modulates Ca2+ sensitivity of human skeletal muscle fibers
- 2016
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 26:5, s. 488-497
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Tidskriftsartikel (refereegranskat)abstract
- The effects of short-term high-intensity exercise on single fiber contractile function in humans are unknown. Therefore, the purposes of this study were: (a) to access the acute effects of repeated high-intensity exercise on human single muscle fiber contractile function; and (b) to examine whether contractile function was affected by alterations in the redox balance. Eleven elite cross-country skiers performed four maximal bouts of 1300m treadmill skiing with 45min recovery. Contractile function of chemically skinned single fibers from triceps brachii was examined before the first and following the fourth sprint with respect to Ca2+ sensitivity and maximal Ca2+-activated force. To investigate the oxidative effects of exercise on single fiber contractile function, a subset of fibers was incubated with dithiothreitol (DTT) before analysis. Ca2+ sensitivity was enhanced by exercise in both MHC I (17%, P<0.05) and MHC II (15%, P<0.05) fibers. This potentiation was not present after incubation of fibers with DTT. Specific force of both MHC I and MHC II fibers was unaffected by exercise. In conclusion, repeated high-intensity exercise increased Ca2+ sensitivity in both MHC I and MHC II fibers. This effect was not observed in a reducing environment indicative of an exercise-induced oxidation of the human contractile apparatus.
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| 5. |
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| 6. |
- Jensen, R., et al.
(författare)
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Heterogeneity in subcellular muscle glycogen utilisation during exercise impacts endurance capacity in men
- 2020
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Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 598:19, s. 4271-4292
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Tidskriftsartikel (refereegranskat)abstract
- Key points: When muscle biopsies first began to be used routinely in research on exercise physiology five decades ago, it soon become clear that the muscle content of glycogen is an important determinant of exercise performance. Glycogen particles are stored in distinct pools within the muscles, but the role of each pool during exercise and how this is affected by diet is unknown. Here, the effects of diet and exercise on these pools, as well as their relation to endurance during prolonged cycling were examined. We demonstrate here that an improved endurance capacity with high carbohydrate loading is associated with a temporal shift in the utilisation of the distinct stores of glycogen pools and is closely linked to the content of the glycogen pool closest to actin and myosin (intramyofibrillar glycogen). These findings highlight the functional importance of distinguishing between different subcellular microcompartments of glycogen in individual muscle fibres. Abstract: In muscle cells, glycogen is stored in three distinct subcellular pools: between or within myofibrils (inter- and intramyofibrillar glycogen, respectively) or beneath the sarcolemma (subsarcolemmal glycogen) and these pools may well have different functions. Here, we investigated the effect of diet and exercise on the content of these distinct pools and their relation to endurance capacity in type 1 and 2 muscle fibres. Following consumption of three different diets (normal, mixed diet = MIX, high in carbohydrate = HIGH, or low in carbohydrate = LOW) for 72 h, 11 men cycled at 75% of (Formula presented.) max until exhaustion. The volumetric content of the glycogen pools in muscle biopsies obtained before, during, and after exercise were quantified by transmission electron micrographs. The mean (SD) time to exhaustion was 150 (30), 112 (22), and 69 (18) minutes in the HIGH, MIX and LOW trials, respectively (P < 0.001). As shown by multiple regression analyses, the intramyofibrillar glycogen content in type 1 fibres, particularly after 60 min of exercise, correlated most strongly with time to exhaustion. In the HIGH trial, intramyofibrillar glycogen was spared during the initial 60 min of exercise, which was associated with levels and utilisation of subsarcolemmal glycogen above normal. In all trials, utilisation of subsarcolemmal and intramyofibrillar glycogen was more pronounced than that of intermyofibrillar glycogen in relative terms. In conclusion, the muscle pool of intramyofibrillar glycogen appears to be the most important for endurance capacity in humans. In addition, a local abundance of subsarcolemmal glycogen reduces the utilisation of intramyofibrillar glycogen during exercise.
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| 7. |
- Ooi, Esther M. M., et al.
(författare)
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Association of apolipoprotein M with high-density lipoprotein kinetics in overweight-obese men
- 2010
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 210:1, s. 326-330
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate associations between plasma apoM concentration and HDL apoA-I and apoA-II kinetics in 60 overweight-obese, insulin resistant men. Methods: Plasma apoM concentration was determined using a sandwich ELISA with two monoclonal antibodies (CV < 5%). The kinetics of HDL apoA-I and apoA-II were measured using intravenous administration of D-3-leucine, gas chromatography-mass spectrometry and multi-compartmental modeling. Results: Plasma apoM was inversely associated with body mass index and positively associated with plasma total cholesterol, LDL cholesterol and HDL cholesterol (p < 0.05). There were no associations between plasma apoM and plasma triglyceride, NEFA, insulin, glucose, HOMA score or adiponectin concentrations. Plasma apoM was positively associated with both apoA-I and apoA-II concentrations (r = 0.406, p < 0.01 and r = 0.510, p < 0.01, respectively) and negatively associated with HDL apoA-I and apoA-II fractional catabolic rate (FCR) (r = -0.291, p = 0.03 and r = -0.291, p = 0.026, respectively). No significant associations were observed between plasma apoM and HDL apoA-I and apoA-II production rate. In multivariate regression models, both plasma apoM and triglycerides were significant, independent predictors of HDL apoA-I FCR (adjusted R-2 = 16%, p < 0.01) and HDL apoA-II FCR (adjusted R-2 = 14%, p < 0.01). Conclusion: ApoM may be a significant, independent predictor of HDL apoA-I and apoA-II catabolism in overweight-obese, insulin resistant men. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.
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| 8. |
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| 9. |
- Plomgaard, P, et al.
(författare)
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Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:10, s. 2939-2945
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Tidskriftsartikel (refereegranskat)abstract
- Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-α (TNF-α) concentrations have been implicated in the development of insulin resistance, but direct evidence in humans is lacking. Here, we demonstrate that TNF-α infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method. TNF-α directly impairs glucose uptake and metabolism by altering insulin signal transduction. TNF-α infusion increases phosphorylation of p70 S6 kinase, extracellular signal–regulated kinase-1/2, and c-Jun NH2-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1. These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake. Thus, excessive concentrations of TNF-α negatively regulate insulin signaling and whole-body glucose uptake in humans. Our results provide a molecular link between low-grade systemic inflammation and the metabolic syndrome.
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| 10. |
- Rostgaard, N., et al.
(författare)
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Differential proteomic profile of lumbar and ventricular cerebrospinal fluid
- 2023
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Ingår i: Fluids and Barriers of the Cns. - : Springer Science and Business Media LLC. - 2045-8118. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.MethodsCSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-beta (A beta(40), A beta(42)), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles.ResultsIn total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer's disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, A beta(40), A beta(42)) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF.ConclusionsThe overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.
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