Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice
Abstract
Interleukin-6 (IL-6) is released from working skeletal muscle during exercise. We investigated the acute and the long-term beneficial effects of IL-6 on exercise-induced glucose uptake in skeletal muscle and insulin sensitivity. The acute effect on exercise-induced glucose uptake was measured in IL-6-deficient (IL-6(-/-)) mice and wild-type control animals using a tracer technique. There was no difference in serum disappearance of (3)[H]2-deoxyglucose after a single bout of exercise between IL-6(-/-) and wild-type mice (13565 ± 426 versus 14343 ± 1309 d.p.m. min ml(-1), P = 0.5). The glucose uptake rate in the extensor digitorum longus muscle was, however, lower in IL-6(-/-) compared with wild-type mice (398 ± 44 versus 657 ± 41 nmol g(-1) min(-1), P < 0.01). In a long-term study, we monitored insulin sensitivity, serum retinol-binding protein-4 (RBP-4) levels, running activity, food intake, body weight and body composition in IL-6(-/-) and wild-type mice on a high-fat diet (HFD), with or without access to running wheels. In sedentary IL-6(-/-) and wild-type mice, the HFD decreased insulin sensitivity (glucose area under the concentration-time curve increased about 20% during an insulin tolerance test, P < 0.05 for both genotypes versus baseline) and led to a 30% increase in serum RBP-4 levels (P < 0.01 for both genotypes versus baseline). Wild-type mice with access to running wheels were protected against these effects of the HFD and maintained their baseline insulin sensitivity and serum RBP-4 levels. In contrast, IL-6(-/-) mice did not benefit from running to the same extent as wild-type animals. The IL-6(-/-) mice with access to running wheels had a similar decrease in insulin sensitivity to their sedentary littermates (glucose area under the concentration-time curve during an insulin tolerance test in runners versus sedentary IL-6(-/-) HFD mice, 312 ± 14 versus 340 ± 22 mmol min l(-1), P = 0.4) and displayed a 14% increase in serum RBP-4 compared with baseline levels (P < 0.01). Our results indicate that endogenous IL-6 contributes to the exercise-induced increase in insulin sensitivity, but plays only a minor role for glucose uptake into skeletal muscle during exercise.
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Aerobic exercise, which also induces IL6, is highly associated with improved outcomes in depression and anxiety.
“On the other hand, aerobic exercise, which also induces IL6 (Benrick et al., 2012; Pedersen and Febbraio, 2008; Reza et al., 2017), is highly associated with improved outcomes in depression and anxiety.”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Benrick et al., 2012
IL-6 KO mice reveal a relatively minor role for IL-6 in promoting glucose clearance during acute treadmill exercise.
“Recently, IL-6 KO mice reveal a relatively minor role for IL-6 in promoting glucose clearance during acute treadmill exercise [167].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [167]
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- Authors
- Benrick, A., Wallenius, V., & Asterholm, I. W.
- Affiliations
- University of Gothenburg (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Asterholm, Ingrid Wernstedt
- Venue
- Experimental Physiology
- Publisher
- Wiley
- Published
- 2012-05-31
- Volume
- 97
- Issue
- 11
- Pages
- 1224-1235
- ISSN
- 0958-0670 (ISSN-L)
- 1469-445X
- OpenAlex
- W1557199979
- Cited by
- 49
- References
- 46
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 10 · 2012: 1
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Svenska Sällskapet för Medicinsk Forskning
- Svenska Läkaresällskapet
- Novo Nordisk Fonden (NNF12OC1016065)
- Sahlgrenska Akademin
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- interleukin-6, physical activity, insulin sensitivity, skeletal muscle glucose uptake, retinol-binding protein 4, high-fat diet, running wheel exercise, IL-6-deficient mice, insulin resistance, adipokines, skeletal muscle inflammation, body composition, insulin tolerance test, extensor digitorum longus, adipose tissue inflammation
- MeSH terms
- Animals, Body Composition, Body Weight, Eating, Female, Glucose, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Physical Conditioning, Animal, Running, Interleukin-6, Muscle, Skeletal, Mice, Retinol-Binding Proteins, Plasma, Diet, High-Fat
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