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- Benrick, Anna, 1979, et al.
(författare)
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Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice.
- 2012
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Ingår i: Experimental physiology. - : Wiley. - 1469-445X .- 0958-0670. ; 97:11 SI, s. 1224-1235
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-6 (IL-6) is released from working skeletal muscle during exercise. We investigated the acute and the long-term beneficial effects of IL-6 on exercise-induced glucose uptake in skeletal muscle and insulin sensitivity. The acute effect on exercise-induced glucose uptake was measured in IL-6 deficient (-/-) mice and wild type controls using a tracer technique. There was no difference in serum disappearance of 3H-2-deoxyglucose after a bolus dose of exercise between IL-6 -/- and wild type mice (13565 ± 426 vs. 14343 ± 1309 dpm*min/ml, p=0.5). The glucose uptake rate in the EDL muscle was however lower in IL-6 -/- compared to wildtype mice (398 ± 44 vs. 657 ± 41 nmol/g/min, p<0.01). In the long-term study, we monitored insulin sensitivity, serum retinol-binding protein-4 (RBP-4) levels, running activity, food intake, body weight and body composition in IL-6 -/- and wild type mice on a high-fat diet (HFD), with or without access to running wheels. In sedentary IL-6 -/- and wild type mice, HFD decreased insulin sensitivity (glucose AUC increased about 20% during an insulin tolerance test (ITT), p<0.05 for both genotypes vs. baseline) and led to a 30% increase in serum RBP-4 levels (p <0.01 for both genotypes vs. baseline). Wild type runners were protected against these effects of HFD and maintained their baseline insulin sensitivity and serum RBP-4 levels. In contrast, IL-6 -/- mice did not, to the same extent as wild types, benefit from running. IL-6 -/- runners had a similar decrease in insulin sensitivity as their sedentary littermates (glucose AUC during an ITT in runners vs. sedentary IL-6-/- HFD mice: 312 ± 14 vs. 340 ± 22 mmol*min/L, p=0.4) and displayed a 14% increase in serum RBP-4 as compared to baseline levels (p<0.01). Our results indicate that endogenous IL-6 contributes to the exercise-induced increase in insulin sensitivity, but only plays a minor role for glucose uptake into skeletal muscle during exercise.
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- Docherty, N. G., et al.
(författare)
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Improvements in the metabolic milieu following Roux-en-Y gastric bypass and the arrest of diabetic kidney disease
- 2014
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 99:9, s. 1146-1153
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Tidskriftsartikel (refereegranskat)abstract
- Roux-en-Y gastric bypass (RYGB) is an efficacious intervention for morbid obesity and has a diabetes-remitting effect in patients with obesity and type 2 diabetes mellitus, which occurs prior to significant weight loss. Roux-en-Y gastric bypass is also associated with early and sustained reductions in the risk factor profile for the progression of diabetic complications. Attention is therefore now being placed on RYGB as a metabolic intervention with the capacity to yield therapeutic benefit in relation to the progression of diabetic complications, such as diabetic kidney disease. As alterations in gut anatomy following RYGB coincide with attendant shifts in downstream enteroendocrine signals with direct and indirect resolutionary effects on the kidney, the concept of an endocrine gut-kidney axis post-RYGB is growing. With the model of a gut-kidney axis in mind, this article summarizes emerging data on the effects of RYGB on risk factors for diabetic kidney disease (hyperglycaemia, dyslipidaemia and hypertension), highlighting a potential role for glucagon-like peptide 1 in risk factor reduction.
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- Essen-Gustavsson, Birgitta, et al.
(författare)
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Muscle glycogen resynthesis, signalling and metabolic responses following acute exercise in exercise-trained pigs carrying the PRKAG3 mutation
- 2011
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 96, s. 927-937
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Tidskriftsartikel (refereegranskat)abstract
- Hampshire pigs carrying the PRKAG3 mutation in the AMP-activated protein kinase (AMPK) gamma(3) subunit exhibit excessive skeletal muscle glycogen storage and an altered glycogen synthesis signalling response following exercise. AMPK plays an important role as a regulator of carbohydrate and fat metabolism in mammalian cells. Exercise-trained muscles are repeatedly exposed to glycogen degradation and resynthesis, to which the signalling pathways adapt. The aim of this study was to examine the effect of acute exercise on glycogen synthesis signalling pathways, and the levels of insulin and other substrates in blood in exercise-trained pigs with and without the PRKAG3 mutation. After 5 weeks of training, pigs performed two standardized treadmill exercise tests, and skeletal muscle biopsies were obtained immediately after exercise and 3 h postexercise in the first test, and 6 h postexercise in the second test. The PRKAG3 mutation carriers had higher glycogen storage, and resynthesis of glycogen was faster after 3 h but not after 6 h of recovery. Alterations in the concentrations of insulin, glucose, lactate and free fatty acids after exercise did not differ between the genotypes. The carriers showed a lower expression of AMPK and increased phosphorylation of Akt Ser(473) after exercise, compared with non-carriers. Acute exercise stimulated the phosphorylation of AS160 in both genotypes, and the phosphorylation of GSK3 alpha Ser(21) and ACC Ser(79) in the non-carriers. In conclusion, exercise-trained pigs carrying the PRKAG3 mutation show an altered Akt and AMPK signalling response to acute exercise, indicating that glucose metabolism is associated with faster resynthesis of muscle glycogen in this group.
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| 6. |
- Feng, Yi, et al.
(författare)
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Electrical and manual acupuncture stimulation affect oestrous cyclicity and neuroendocrine function in an 5α-dihydrotestosterone-induced rat polycystic ovary syndrome model.
- 2012
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Ingår i: Experimental physiology. - : Wiley. - 1469-445X .- 0958-0670. ; 97:5, s. 651-62
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Tidskriftsartikel (refereegranskat)abstract
- Both low-frequency electro-acupuncture (EA) and manual acupuncture improve menstrual frequency and decrease circulating androgens in women with polycystic ovary syndrome (PCOS). We sought to determine whether low-frequency EA is more effective than manual stimulation in regulating disturbed oestrous cyclicity in rats with PCOS induced by 5α-dihydrotestosterone. To identify the central mechanisms of the effects of stimulation, we assessed hypothalamic mRNA expression of molecules that regulate reproductive and neuroendocrine function. From age 70 days, rats received 2 Hz EA or manual stimulation with the needles five times per week for 4-5 weeks; untreated rats served as control animals. Specific hypothalamic nuclei were obtained by laser microdissection, and mRNA expression was measured with TaqMan low-density arrays. Untreated rats were acyclic. During the last 2 weeks of treatment, seven of eight (88%) rats in the EA group had epithelial keratinocytes, demonstrating oestrous cycle change (P = 0.034 versus control rats). In the manual group, five of eight (62%) rats had oestrous cycle changes (n.s. versus control animals). The mRNA expression of the opioid receptors Oprk1 and Oprm1 in the hypothalamic arcuate nucleus was lower in the EA group than in untreated control rats. The mRNA expression of the steroid hormone receptors Esr2, Pgr and Kiss1r was lower in the manual group than in the control animals. In rats with 5α-dihydrotestosterone-induced PCOS, low-frequency EA restored disturbed oestrous cyclicity but did not differ from the manual stimulation group, although electrical stimulation lowered serum testosterone in responders, those with restored oestrus cyclicity, and differed from both control animals and the manual stimulation group. Thus, EA cannot in all aspects be considered superior to manual stimulation. The effects of low-frequency EA may be mediated by central opioid receptors, while manual stimulation may involve regulation of steroid hormone/peptide receptors.
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| 9. |
- Krivickas, Lisa S., et al.
(författare)
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Relationship between force and size in human single muscle fibres
- 2011
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 96:5, s. 539-547
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Tidskriftsartikel (refereegranskat)abstract
- When the contractile properties of single muscle fibres are studied, force is typically normalized by fibre cross-sectional area and expressed as specific force. We studied a set of 2725 chemically skinned human single muscle fibres from 119 healthy adults to determine whether specific force is the optimal way to express the relationship between single-fibre force and size. A linear mixed effects model was used to estimate the slope and slope variability among individuals of log-log plots of force and diameter. For type I fibres, the slope estimate was 0.99 (95% confidence interval 0.36-1.62), and for type IIa fibres it was 0.94 (95% confidence interval 0.77-1.11), indicating that force is proportional to fibre diameter, rather than to cross-sectional area. If force were proportional to cross-sectional area, the slope estimate would be 2.0. In future studies using the chemically skinned single fibre preparation, force may be normalized to fibre diameter rather than cross-sectional area. We propose that a new term, 'normalized force', be used for this variable, with units of newtons per metre. We demonstrate using our data set that when populations of single fibres are compared with one another, the determination of whether the size and force relationship is the same or different is dependent upon the method used to account for fibre size (i.e. specific force versus 'normalized force').
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| 10. |
- le Roux, Carel W, et al.
(författare)
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The physiology of altered eating behaviour after Roux-en-Y gastric bypass
- 2014
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 99:9, s. 1128-1132
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and its related comorbidities can be detrimental for the affected individual, as well as constituting a major challenge to public health systems worldwide. Currently, the most effective treatment option leading to clinically significant and maintained body weight loss and reduction in obesity-related morbidity and mortality is obesity surgery, which is recommended for patients with a body mass index of >40 kg m(-2), or >35 kg m(-2) if obesity-associated comorbidities, such as type 2 diabetes mellitus, are present. This report focuses on the altered eating behaviour after the most common of these operations, the Roux-en-Y gastric bypass. Animal and human experiments designed to understand the underlying physiological mechanisms of altered taste and appetite are discussed.
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