17 research outputs found

    Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes : a randomised crossover trial

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    Data availability The data analysed during the current study are available from the corresponding author on reasonable request. Funding The authors are supported by grants from Novo Nordisk Foundation (NNF14OC0011493 and NNF14OC0009941), Swedish Diabetes Foundation (DIA2015-052), Wenner-Gren Foundation, Swedish Research Council (2015-00165), Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), Stockholm County Council (SLL20150517 and SLL20170159) and Swedish Heart Lung Foundation (20150423).Peer reviewedPublisher PD

    Three weeks of interrupting sitting lowers fasting glucose and glycemic variability, but not glucose tolerance, in free-living women and men with obesity

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    Funding This work was supported by grants from the Novo Nordisk Foundation (NNF14OC0011493, NNF14OC0009941, NNF18CC0034900), Swedish Diabetes Foundation (DIA2018-357), Diabetes Wellness Sverige (1849-PG), Swedish Research Council (2015-00165, 2018-02389), the Strategic Research Programme in Diabetes at Karolinska Institutet (2009-1068), the Knut and Alice Wallenberg Foundation (2018-0094), and the Stockholm County Council (SLL20170159). D.D. is supported by the National Health and Medical Research Council and the Victorian Government’s OIS scheme. Acknowledgements We thank the Swedish Metabolomics Centre (UmeĂ„ University) for assisting with the lipidomic analysis and Mariam Nordstrand for efforts in the recruitment and screening of participants, and in muscle biopsy procedure. The current addresses for S.P. and B.M.G. are the School of Life Sciences, University of Nottingham, Nottingham, UK, and The Rowett Institute, University of Aberdeen, Aberdeen, UK, respectively.Peer reviewedPostprin

    Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle

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    Succinate is released by skeletal muscle during exercise and activates SUCNR1/GPR91. Signaling of SUCNR1 is involved in metabolite-sensing paracrine communication in skeletal muscle during exercise. However, the specific cell types responding to succinate and the directionality of communication are unclear. We aim to characterize the expression of SUCNR1 in human skeletal muscle. De novo analysis of transcriptomic datasets demonstrated that SUCNR1 mRNA is expressed in immune, adipose, and liver tissues, but scarce in skeletal muscle. In human tissues, SUCNR1 mRNA was associated with macrophage markers. Single-cell RNA sequencing and fluorescent RNAscope demonstrated that in human skeletal muscle, SUCNR1 mRNA is not expressed in muscle fibers but coincided with macrophage populations. Human M2-polarized macrophages exhibit high levels of SUCNR1 mRNA and stimulation with selective agonists of SUCNR1 triggered Gq- and Gi-coupled signaling. Primary human skeletal muscle cells were unresponsive to SUCNR1 agonists. In conclusion, SUCNR1 is not expressed in muscle cells and its role in the adaptive response of skeletal muscle to exercise is most likely mediated via paracrine mechanisms involving M2-like macrophages within the muscle. NEW & NOTEWORTHY Macrophages but not skeletal muscle cells respond to extracellular succinate via SUCNR1/GPR91

    Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism

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    We acknowledge the Beta Cell in-vivo Imaging/Extracellular Flux Analysis core facility, supported by the Strategic Research Program (SRP) in Diabetes, for the use of the Seahorse flux analyzer. AUTHOR CONTRIBUTIONS A.M.A. and N.J.P. conceived and designed research; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., and N.J.P. performed experiments; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., and N.J.P. analyzed data; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. interpreted results of experiments; A.M.A. and N.J.P. prepared figures; A.M.A. and N.J.P. drafted manuscript; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. edited and revised manuscript; A.M.A., L.S.P., J.A.B.S., B.M.G., M.S., L.D., A.V.C., A.K., J.R.Z., and N.J.P. approved final version of manuscript.Peer reviewedPublisher PD

    A Multidisciplinary Evaluation of a Virtually Supervised Home-Based High-Intensity Interval Training Intervention in People With Type 1 Diabetes.

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    OBJECTIVE: Adopt a multidisciplinary approach to evaluate a virtually supervised home-based high-intensity interval training (Home-HIT) intervention in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eleven individuals with type 1 diabetes (seven women; age 30 ± 3 years; VO2peak 2.5 ± 0.2 L/min; duration of diabetes 10 ± 2 years) completed 6 weeks of Home-HIT. A heart rate monitor and mobile phone application were used to provide feedback to the participants and research team on exercise intensity (compliance) and adherence. RESULTS: Training adherence was 95 ± 2%, and compliance was 99 ± 1%. Home-HIT increased VO2peak by 7% (P = 0.017) and decreased insulin dose by 13% (P = 0.012). Blood glucose concentration did not change from baseline to immediately or 1 h post Home-HIT. Qualitative perceptions of Home-HIT and the virtual-monitoring system were positive, supporting that the intervention successfully removed exercise barriers in people with type 1 diabetes. CONCLUSIONS: Virtually monitored Home-HIT resulted in high adherence alongside increased VO2peak and decreased insulin dose

    Cellular and molecular mechanisms of skeletal muscle atrophy after spinal cord injury

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    Spinal cord injury leads to a rapid and profound loss of skeletal muscle mass. Muscle atrophy consequently promotes metabolic disturbances and leads to increased risk of type 2 diabetes and cardiovascular disease. Prevention of such consequences requires a deeper understanding of underlying molecular and cellular changes, which promote muscle atrophy. This thesis attempts to elucidate some of the mechanisms responsible for muscle atrophy induced by spinal cord injury; specifically, changes in the abundance of regulators of protein metabolism and enzymes responsible for oxidative stress homeostasis in skeletal muscle. Additionally, we examined the impact of spinal cord injury on the differentiation capacity of satellite cells, measured in vitro. Our results suggest most profound changes in skeletal muscle within the first three months post-injury, including higher reactive oxygen species production, apoptosis, and protein turnover. Conversely, we show retained intrinsic satellite cell differentiation capacity, despite substantial changes within skeletal muscle. Collectively, the studies in this thesis encourage efforts to maintain protein metabolism balance and oxidative stress homeostasis during the early post-spinal cord injury phases, as well as rehabilitative interventions targeting satellite cell activation

    Altered oxidative stress and antioxidant defence in skeletal muscle during the first year following spinal cord injury

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    Oxidative stress promotes protein degradation and apoptosis in skeletal muscle undergoing atrophy. We aimed to determine whether spinal cord injury leads to changes in oxidative stress, antioxidant capacity, and apoptotic signaling in human skeletal muscle during the first year after spinal cord injury. Vastus lateralis biopsies were obtained from seven individuals 1, 3, and 12 months after spinal cord injury and from seven able‐bodied controls. Protein content of enzymes involved in reactive oxygen species production and detoxification, and apoptotic signaling were analyzed by western blot. Protein carbonylation and 4‐hydroxynonenal protein adducts were measured as markers of oxidative damage. Glutathione content was determined fluorometrically. Protein content of NADPH oxidase 2, xanthine oxidase, and pro‐caspase‐3 was increased at 1 and 3 months after spinal cord injury compared to able‐bodied controls. Furthermore, total and reduced glutathione content was increased at 1 and 3 months after spinal cord injury. Conversely, mitochondrial complexes and superoxide dismutase 2 protein content were decreased 12 months after spinal cord injury compared to able‐bodied controls. In conclusion, we provide indirect evidence of increased reactive oxygen species production and increased apoptotic signaling at 1 and 3 months after spinal cord injury. Concomitant increases in glutathione antioxidant defences may reflect adaptations poised to maintain redox homeostasis in skeletal muscle following spinal cord injury
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