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Träfflista för sökning "WFRF:(Wojtaszewski Jörgen F. P.) "

Sökning: WFRF:(Wojtaszewski Jörgen F. P.)

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1.
  • Fritzen, Andreas Mæchel, et al. (författare)
  • ApoA-1 improves glucose tolerance by increasing glucose uptake into heart and skeletal muscle independently of AMPKα2
  • 2020
  • Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 35
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Acute administration of the main protein component of high-density lipoprotein, apolipoprotein A-I (ApoA-1), improves glucose uptake in skeletal muscle. The molecular mechanisms mediating this are not known, but in muscle cell cultures, ApoA-1 failed to increase glucose uptake when infected with a dominant-negative AMP-activated protein kinase (AMPK) virus. We therefore investigated whether AMPK is necessary for ApoA-1-stimulated glucose uptake in intact heart and skeletal muscle in vivo. Methods: The effect of injection with recombinant human ApoA-1 (rApoA-1) on glucose tolerance, glucose-stimulated insulin secretion, and glucose uptake into skeletal and heart muscle with and without block of insulin secretion by injection of epinephrine (0.1 mg/kg) and propranolol (5 mg/kg), were investigated in 8 weeks high-fat diet-fed (60E%) wild-type and AMPKα2 kinase-dead mice in the overnight-fasted state. In addition, the effect of rApoA-1 on glucose uptake in isolated skeletal muscle ex vivo was studied. Results: rApoA-1 lowered plasma glucose concentration by 1.7 mmol/l within 3 h (6.1 vs 4.4 mmol/l; p < 0.001). Three hours after rApoA-1 injection, glucose tolerance during a 40-min glucose tolerance test (GTT) was improved compared to control (area under the curve (AUC) reduced by 45%, p < 0.001). This was accompanied by an increased glucose clearance into skeletal (+110%; p < 0.001) and heart muscle (+100%; p < 0.001) and an increase in glucose-stimulated insulin secretion 20 min after glucose injection (+180%; p < 0.001). When insulin secretion was blocked during a GTT, rApoA-1 still enhanced glucose tolerance (AUC lowered by 20% compared to control; p < 0.001) and increased glucose clearance into skeletal (+50%; p < 0.05) and heart muscle (+270%; p < 0.001). These improvements occurred to a similar extent in both wild-type and AMPKα2 kinase-dead mice and thus independently of AMPKα2 activity in skeletal- and heart muscle. Interestingly, rApoA-1 failed to increase glucose uptake in isolated skeletal muscles ex vivo. Conclusions: In conclusion, ApoA-1 stimulates in vivo glucose disposal into skeletal and heart muscle independently of AMPKα2. The observation that ApoA-1 fails to increase glucose uptake in isolated muscle ex vivo suggests that additional systemic effects are required.
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2.
  • Thorell, Anders, et al. (författare)
  • Exerciseand insulin cause GLUT-4 translocation in human skeletal muscle
  • 1999
  • Ingår i: American Journal of Physiology. - : American Physiological Society. - 0002-9513 .- 2163-5773. ; 277:4, s. E733-E741
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocationphenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic- hyperinsulinemic clamp (0.8 mU · kg-1 · min-1). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (VO(2max)), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin(44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased inresponse to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological conditions, moderate intensity exercise and physiological hyperinsulinemia ~56 μU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle.
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3.
  • Davegårdh, Cajsa, et al. (författare)
  • Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects
  • 2017
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:1, s. 1-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. Methods: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model. Results: We observed genome-wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic mice had reduced insulin response and muscle weight. Remarkably, approximately 3.7 times more methylation changes (147,161 versus 39,572) were observed during differentiation of myoblasts from obese versus non-obese subjects. In accordance, DNMT1 expression increased during myogenesis only in obese subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects. Conclusions: Our study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic epigenome during differentiation of human muscle stem cells and reveals abnormal epigenetic changes in obesity.
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4.
  • Treebak, Jonas T, et al. (författare)
  • AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
  • 2006
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:7, s. 2051-2058
  • Tidskriftsartikel (refereegranskat)abstract
    • AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-D-ribonucleoside (AICAR). AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle. Recombinant AMPK heterotrimeric complexes (alpha 1 beta 1 gamma l and alpha 2 beta 2 gamma 1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha 2 AMPK knockout [KO], alpha 2 AMPK kinase dead [KD], and gamma 3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha 2 and gamma 3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha 2 AMPK KO and KD but not gamma 3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.
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