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Published in: Diabetologia 7/2024

Open Access 25-04-2024 | Insulins | Article

Exercise-induced increase in muscle insulin sensitivity in men is amplified when assessed using a meal test

Authors: Christian T. Voldstedlund, Kim A. Sjøberg, Farina L. Schlabs, Casper M. Sigvardsen, Nicoline R. Andersen, Jens J. Holst, Bolette Hartmann, Jørgen F. P. Wojtaszewski, Bente Kiens, Glenn K. McConell, Erik A. Richter

Published in: Diabetologia | Issue 7/2024

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Exercise has a profound effect on insulin sensitivity in skeletal muscle. The euglycaemic–hyperinsulinaemic clamp (EHC) is the gold standard for assessment of insulin sensitivity but it does not reflect the hyperglycaemia that occurs after eating a meal. In previous EHC investigations, it has been shown that the interstitial glucose concentration in muscle is decreased to a larger extent in previously exercised muscle than in rested muscle. This suggests that previously exercised muscle may increase its glucose uptake more than rested muscle if glucose supply is increased by hyperglycaemia. Therefore, we hypothesised that the exercise-induced increase in muscle insulin sensitivity would appear greater after eating a meal than previously observed with the EHC.


Ten recreationally active men performed dynamic one-legged knee extensor exercise for 1 h. Following this, both femoral veins and one femoral artery were cannulated. Subsequently, 4 h after exercise, a solid meal followed by two liquid meals were ingested over 1 h and glucose uptake in the two legs was measured for 3 h. Muscle biopsies from both legs were obtained before the meal test and 90 min after the meal test was initiated. Data obtained in previous studies using the EHC (n=106 participants from 13 EHC studies) were used for comparison with the meal-test data obtained in this study.


Plasma glucose and insulin peaked 45 min after initiation of the meal test. Following the meal test, leg glucose uptake and glucose clearance increased twice as much in the exercised leg than in the rested leg; this difference is twice as big as that observed in previous investigations using EHCs. Glucose uptake in the rested leg plateaued after 15 min, alongside elevated muscle glucose 6-phosphate levels, suggestive of compromised muscle glucose metabolism. In contrast, glucose uptake in the exercised leg plateaued 45 min after initiation of the meal test and there were no signs of compromised glucose metabolism. Phosphorylation of the TBC1 domain family member 4 (TBC1D4; p-TBC1D4Ser704) and glycogen synthase activity were greater in the exercised leg compared with the rested leg. Muscle interstitial glucose concentration increased with ingestion of meals, although it was 16% lower in the exercised leg than in the rested leg.


Hyperglycaemia after meal ingestion results in larger differences in muscle glucose uptake between rested and exercised muscle than previously observed during EHCs. These findings indicate that the ability of exercise to increase insulin-stimulated muscle glucose uptake is even greater when evaluated with a meal test than has previously been shown with EHCs.

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Exercise-induced increase in muscle insulin sensitivity in men is amplified when assessed using a meal test
Christian T. Voldstedlund
Kim A. Sjøberg
Farina L. Schlabs
Casper M. Sigvardsen
Nicoline R. Andersen
Jens J. Holst
Bolette Hartmann
Jørgen F. P. Wojtaszewski
Bente Kiens
Glenn K. McConell
Erik A. Richter
Publication date
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2024
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428

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