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Träfflista för sökning "LAR1:gu ;pers:(Ohlsson Claes 1965);pers:(Svensson Johan 1964)"

Sökning: LAR1:gu > Ohlsson Claes 1965 > Svensson Johan 1964

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1.
  • Iresjö, Britt-Marie, 1963-, et al. (författare)
  • Liver-derived endocrine IGF-I is not critical for activation of skeletal muscle protein synthesis following oral feeding.
  • 2013
  • Ingår i: BMC physiology. - 1472-6793. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Insulin-like growth factor-1 (IGF-1) is produced in various tissues to stimulate protein synthesis under different conditions. It is however, difficult to distinguish effects by locally produced IGF-1 compared to liver-derived IGF-1 appearing in the circulation. In the present study the role of liver-derived endocrine IGF-I for activation of skeletal muscle protein synthesis following feeding was evaluated. RESULTS: Transgenic female mice with selective knockout of the IGF-I gene in hepatocytes were freely fed, starved overnight and subsequently refed for 3 hours and compared to wild types (wt). Liver IGF-I knockout mice had 70% reduced plasma IGF-I. Starvation decreased and refeeding increased muscle protein synthesis (p < 0.01), similarly in both IGF-I knockouts and wt mice. Phosphorylation of p70s6k and mTOR increased and 4EBP1 bound to eIF4E decreased in both IGF-I knockouts and wt mice after refeeding (p < 0.05). Muscle transcripts of IGF-I decreased and IGF-I receptor increased (p < 0.01) in wild types during starvation but similar alterations did not reach significance in knockouts (p>0.05). mTOR mRNA increased in knockouts only during starvation. Plasma glucose decreased during starvation in all groups in parallel to insulin, while plasma IGF-I and GH did not change significantly among the groups during starvation-refeeding. Plasma amino acids declined and increased during starvation-refeeding in wild type mice (p < 0.05), but less so in IGF-I (-/-) knockouts (p < 0.08). CONCLUSION: This study demonstrates that re-synthesis of muscle proteins following starvation is not critically dependent on endocrine liver-derived IGF-I.
2.
  • Johansson, Per, 1966-, et al. (författare)
  • Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
  • 2011
  • Ingår i: Clinical endocrinology. - 1365-2265. ; 75:3, s. 301-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and Patients: A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements: Sex steroid and precursor levels were determined in serum and when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results: Patients in the D group had higher 24-h urine cortisol level and increased serum levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, androsterone (ADT), and estrone (E1) and its sulfate ester E1S, compared to the controls. When men and women were analyzed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions: In both D men and women, serum E1 and E1S levels were increased whereas other changes were gender-specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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3.
  • Movérare-Skrtic, Sofia, 1976-, et al. (författare)
  • Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.
  • 2006
  • Ingår i: Obesity (Silver Spring, Md.). - 1930-7381. ; 14:4, s. 662-72
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men. RESEARCH METHODS AND PROCEDURES: Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. RESULTS: DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production. DISCUSSION: We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.
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4.
  • Movérare-Skrtic, Sofia, 1976-, et al. (författare)
  • Serum insulin-like growth factor-I concentration is associated with leukocyte telomere length in a population-based cohort of elderly men.
  • 2009
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 94:12, s. 5078-84
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Both leukocyte telomere length and IGF-I are associated with the aging process. A previous in vitro study suggested that IGF-I may modulate telomerase activity in white blood cells, but little is known whether these two systems interact in vivo. PATIENTS AND METHODS: Leukocyte telomere length was determined using a quantitative PCR assay in 2744 elderly men (mean age 75.5 yr, range 69-81 yr) included in the population-based Osteoporotic Fractures in Men-Sweden study. Serum IGF-I concentration was measured using RIA. RESULTS: Subjects with a leukocyte telomere length in the lowest tertile group had lower serum IGF-I concentration than subjects in the two tertile groups with longer telomere lengths (P = 0.005). Logistic regression analyses showed that a higher serum IGF-I concentration was associated with a significantly reduced risk of having a leukocyte telomere length in the lowest tertile group and also after adjustment for multiple covariates (P &lt; 0.01). Multivariate linear regression analyses demonstrated that tertile of leukocyte telomere length was positively, whereas age was negatively, associated with serum IGF-I concentration in elderly men. CONCLUSIONS: In this large population-based, cross-sectional study, leukocyte telomere length was positively associated with serum IGF-I concentration in elderly men. The mechanisms underlying the association between serum IGF-I concentration and leukocyte telomere length remain to be determined.
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5.
  • Ohlsson, Claes, 1965-, et al. (författare)
  • The role of liver-derived insulin-like growth factor-I.
  • 2009
  • Ingår i: Endocrine reviews. - 1945-7189. ; 30:5, s. 494-535
  • Forskningsöversikt (refereegranskat)abstract
    • IGF-I is expressed in virtually every tissue of the body, but with much higher expression in the liver than in any other tissue. Studies using mice with liver-specific IGF-I knockout have demonstrated that liver-derived IGF-I, constituting a major part of circulating IGF-I, is an important endocrine factor involved in a variety of physiological and pathological processes. Detailed studies comparing the impact of liver-derived IGF-I and local bone-derived IGF-I demonstrate that both sources of IGF-I can stimulate longitudinal bone growth. We propose here that liver-derived circulating IGF-I and local bone-derived IGF-I to some extent have overlapping growth-promoting effects and might have the capacity to replace each other (= redundancy) in the maintenance of normal longitudinal bone growth. Importantly, and in contrast to the regulation of longitudinal bone growth, locally derived IGF-I cannot replace (= lack of redundancy) liver-derived IGF-I for the regulation of a large number of other parameters including GH secretion, cortical bone mass, kidney size, prostate size, peripheral vascular resistance, spatial memory, sodium retention, insulin sensitivity, liver size, sexually dimorphic liver functions, and progression of some tumors. It is clear that a major role of liver-derived IGF-I is to regulate GH secretion and that some, but not all, of the phenotypes in the liver-specific IGF-I knockout mice are indirect, mediated via the elevated GH levels. All of the described multiple endocrine effects of liver-derived IGF-I should be considered in the development of possible novel treatment strategies aimed at increasing or reducing endocrine IGF-I activity.
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6.
  • Scharin Täng, Margareta, 1962-, et al. (författare)
  • Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling
  • 2012
  • Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - 1096-6374. ; 22:6, s. 206-211
  • Tidskriftsartikel (refereegranskat)abstract
    • IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI.
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7.
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8.
  • Svensson, Johan, 1964-, et al. (författare)
  • Effects of growth hormone and its secretagogues on bone.
  • 2001
  • Ingår i: Endocrine. - 0969-711X. ; 14:1, s. 63
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.
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9.
  • Svensson, Johan, 1964-, et al. (författare)
  • Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice.
  • 2006
  • Ingår i: The Journal of endocrinology. - 0022-0795. ; 189:3, s. 617
  • Tidskriftsartikel (refereegranskat)abstract
    • IGF-I is a neuroprotective hormone, and neurodegenerative disorders, including Alzheimer's disease, have been associated with decreased serum IGF-I concentration. In this study, IGF-I production was inactivated in the liver of adult mice (LI-IGF-I(-/-)), resulting in an approximately 80-85% reduction of circulating IGF-I concentrations. In young (6-month-old) mice there was no difference between the LI-IGF-I(-/-) and the control mice in spatial learning and memory as measured using the Morris water maze test. In old (aged 15 and 18 months) LI-IGF-I(-/-) mice, however, the acquisition of the spatial task was slower than in the controls. Furthermore, impaired spatial working as well as reference memory was observed in the old LI-IGF(-/-) mice. Histochemical analyses revealed an increase in dynorphin and enkephalin immunoreactivities but decreased mRNA levels in the hippocampus of old LI-IGF-I(-/-) mice. These mice also displayed astrocytosis and increased metabotropic glutamate receptor 7a-immunoreactivity. These neurochemical disturbances suggest synaptic dysfunction and early neurodegeneration in old LI-IGF-I(-/-) mice. The decline in serum IGF-I with increasing age may therefore be important for the age-related decline in memory function.
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10.
  • Svensson, Johan, 1964-, et al. (författare)
  • Liver-derived IGF-I regulates exploratory activity in old mice.
  • 2005
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 289:3, s. 466-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth hormone (GH) replacement in hypopituitary patients improves well-being and initiative. Experimental studies indicate that these psychic effects may be reflected in enhanced locomotor activity in mice. It is unknown whether these phenomena are mediated directly by GH or by circulating IGF-I. IGF-I production in the liver was inactivated at 6-10 wk of age (LI-IGF-I-/- mice), resulting in an 80-85% reduction of circulating IGF-I, and, secondary to this, increased GH secretion. Using activity boxes on three different occasions during 1 wk, 6-mo-old LI-IGF-I-/- mice had similar activity levels, and 14-mo-old mice had a moderate but significant decrease in activity level, compared with control mice. At 20 mo of age, the LI-IGF-I-/- mice displayed a more prominent decrease in activity level with decreased horizontal activity throughout the test period, and at day 1, there were several signs of an altered habituation process with different time patterns of locomotor activity and horizontal activity compared with the control mice. At days 3 and 5, rearing activity was lower in the 20-mo-old LI-IGF-I-/- mice. Anxiety level was unaffected in all age groups, as measured using the Montgomery's elevated plus-maze. In conclusion, old LI-IGF-I-/- mice displayed a decrease in both horizontal and rearing (exploratory) activity level and an altered habituation process. These results indicate that liver-derived IGF-I mediates at least part of the effects of GH on exploratory activity in mice.
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