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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01249

Effects of exercise training and IL-6 receptor blockade on gastric emptying and GLP-1 secretion in obese humans: Secondary analyses from a double blind randomized clinical trial

 Louise L. Lehrskov1, 2*, Regitse H. Christensen2,  Anne-Sophie Wedell-Neergaard2, Grit E. Legaard2, Emma Dorph2, Monica K. Larsen2, Marie Henneberg2, Natja Launbo2, Sabrina R. Fagerlind2, sidsel K. Seide2, Stine Nymand2, Maria Ball2, Nicole Vinum2, Camilla Dahl2,  Nicolai J. Wewer Albrechtsen3,  Jens Holst3,  Mathias Ried-Larsen2, Jaya B. Rosenmeier2, Rikke Krogh-Madsen2, Kristian Karstoft2, Bente K. Pedersen2 and Helga Ellingsgaard2
  • 1Rigshospitalet, Denmark
  • 2Centre of Inflammation and Metabolism (CIM), Denmark
  • 3Department for Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

Background: Interleukin-6 (IL-6) is released from skeletal muscle during exercise and systemic IL-6 levels therefore increase acutely in response to a single bout of exercise. We recently showed that an acute increase in IL-6 delayed gastric emptying rate and improved postprandial glycemia. Here we investigate whether repeated increases in IL-6, induced by exercise training, influence gastric emptying rate and moreover if IL-6 is required for exercise-induced adaptations in glycemic control including secretion of glucagon and glucagon-like peptide-1 (GLP-1).
Methods: 52 abdominally obese non-diabetic men and women were randomly assigned into four groups performing 12 weeks of endurance exercise or no exercise with or without IL-6 receptor blockade (tocilizumab). The primary endpoint was change in gastric emptying rate in response to the intervention and other endpoints included changes in glycemic control, glucagon and GLP-1 secretion.
Results: There was no change in gastric emptying rate in any of the four groups following the intervention and comparing differences in change between groups also revealed no difference. Postprandial glucose remained unchanged in all groups but the exercise + tocilizumab group, which improved postprandial glucose in response to the intervention. The area under the curve for meal-stimulated glucagon, active and total GLP-1 increased in response to IL-6 receptor blockade, this effect was independent of exercise.
Conclusion: Exercise training and long-term IL-6 receptor blockade did not change gastric emptying rates in obese humans. IL-6 receptor blockade increased glucagon and GLP-1 secretion and implicate IL-6 in the regulation of the human alpha and L cells.

Keywords: Interleukin-6, Gastric Emptying, Exercise, tocilizumab, Glucagon, GLP-1, Postprandial glucose

Received: 19 Mar 2019; Accepted: 12 Sep 2019.

Copyright: © 2019 Lehrskov, Christensen, Wedell-Neergaard, Legaard, Dorph, Larsen, Henneberg, Launbo, Fagerlind, Seide, Nymand, Ball, Vinum, Dahl, Wewer Albrechtsen, Holst, Ried-Larsen, Rosenmeier, Krogh-Madsen, Karstoft, Pedersen and Ellingsgaard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Louise L. Lehrskov, Rigshospitalet, Copenhagen, Denmark, louise.lang.lehrskov.01@regionh.dk