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

TY - JOUR

T1 - 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

AU - Lehrskov, Louise Lang

AU - Christensen, Regitse Hojgaard

AU - Wedell-Neergaard, Anne-Sophie

AU - Legaard, Grit Elster

AU - Dorph, Emma

AU - Larsen, Monica Korsager

AU - Henneberg, Marie

AU - Launbo, Natja

AU - Fagerlind, Sabrina Ravn

AU - Seide, Sidsel Kofoed

AU - Nymand, Stine

AU - Ball, Maria

AU - Vinum, Nicole

AU - Dahl, Camilla

AU - Albrechtsen, Nicolai Jacob Wewer

AU - Holst, Jens Juul

AU - Ried-Larsen, Mathias

AU - Rosenmeier, Jaya Birgitte

AU - Krogh-Madsen, Rikke

AU - Karstoft, Kristian

AU - Pedersen, Bente Klarlund

AU - Ellingsgaard, Helga

PY - 2019/10/4

Y1 - 2019/10/4

N2 - 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: A total of 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.

AB - 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: A total of 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.

KW - interleukin-6

KW - gastric emptying

KW - exercise

KW - tocilizumab

KW - glucagon

KW - GLP-1

U2 - 10.3389/fphys.2019.01249

DO - 10.3389/fphys.2019.01249

M3 - Journal article

C2 - 31636570

SN - 1664-042X

VL - 10

JO - Frontiers in Physiology

JF - Frontiers in Physiology

M1 - 1249

ER -