Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells
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Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.
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IL-6 increases GLP-1 production from proglucagon in pancreatic α-cells and its secretion from α-cells and intestinal L-cells, resulting in GLP-1-mediated increase in insulin secretion.
“Furthermore, IL-6 increased GLP-1 production from proglucagon in pancreatic α-cells and its secretion from α-cells and intestinal L-cells, eventually resulting in a GLP-1-mediated increase in insulin secretion.289”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [289]
IL-6 directly increases GLP-1 in mice and stimulates the sympathetic nervous system, increasing white adipose tissue lipolysis and browning and brown adipose tissue thermogenesis.
“It has been shown to directly increase GLP-1 in mice [73] and to stimulate SNS, increasing WAT lipolysis and “browning” and BAT thermogenesis [19].”
SkM-derived IL-6 stimulates the release of GLP-1.
“SkM-derived IL-6 was described to stimulate the release of GLP-1 [73] (3a)”
In the pancreas, IL-6 stimulates insulin secretion by beta cells by upregulating glucagon-like peptide-1 (GLP-1).
“In the pancreas, IL-6 stimulates insulin secretion by beta cells by upregulating glucagon-like peptide-1 (GLP-1) [85].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [85]
The insulin-secretion benefits of IL-6 have been observed in several rodent models of type 2 diabetes.
“These benefits of IL-6 in enhancing insulin secretion were seen across multiple rodent models of T2DM119.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [119]
In rodents, raising IL-6 through exercise or injection boosts GLP-1 production by intestinal L cells and pancreatic α-cells, which enhances glucose-stimulated insulin secretion.
“In rodents, increasing IL-6 by exercise or by IL-6 injection increases the production of glucagon-like peptide 1 by intestinal L cells and pancreatic α-cells to enhance glucose-stimulated insulin secretion.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [119]
IL-6 is important for insulin secretion and glucose tolerance via glucagon like peptide 1 (GLP-1).
“Nonetheless finding from these studies have shown that IL-6 is important for insulin secretion and glucose tolerance via glucagon like peptide 1 (GLP-1) [169].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [169]
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- [12]Weigert C Lehmann R Schleicher ED Point-counterpoint: interleukin-6 does/does not have a beneficial role in insulin sensitivity and glucose homeostasis J. Appl. Physiol 2007 102 820 821 author reply 825 17323462
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Lebherz, C., Schlieper, G., Möllmann, J., Kahles, F., Schwarz, M., Brünsing, J., Dimkovic, N., Koch, A., Trautwein, C., Flöge, J., et al. (2017) · The American Journal of Medicine · doi:10.1016/j.amjmed.2017.03.010 · Cited by 65 · see citing works
Altered Response of Skeletal Muscle to IL-6 in Type 2 Diabetic Patients
Jiang, L. Q., Duque-Guimaraes, D. E., Machado, U. F., Zierath, J. R., & Krook, A. (2013) · Diabetes · doi:10.2337/db11-1790 · Cited by 65 · see citing works
Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion
Holter, M. M., Saikia, M., & Cummings, B. P. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.934775 · Cited by 63 · see citing works
Selective stimulation of colonic L cells improves metabolic outcomes in mice
Lewis, J. E., Miedzybrodzka, E. L., Foreman, R. E., Woodward, O. R. M., Kay, R. G., Goldspink, D. A., Gribble, F. M., & Reimann, F. (2020) · Diabetologia · doi:10.1007/s00125-020-05149-w · Cited by 59 · see citing works
Self-citationEvolving Concepts and Translational Relevance of Enteroendocrine Cell Biology
Drucker, D. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3449 · Cited by 63 · see citing works
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Qi, C., Song, X., Wang, H., Yan, Y., & Liu, B. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.981577 · Cited by 63 · see citing works
Glucagon-like peptide-1 receptor agonists and muscle mass effects
Ceasovschih, A., Asaftei, A., Lupo, M. G., Kotlyarov, S., Bartušková, H., Balta, A., Sorodoc, V., Sorodoc, L., & Banach, M. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107927 · Cited by 64 · see citing works
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Chen, Z.-T., Weng, Z.-X., Lin, J. D., & Meng, Z.-X. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae006 · Cited by 58 · see citing works
Pang, J., Feng, J. N., Ling, W., & Jin, T. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.06.003 · Cited by 52 · see citing works
Brakenridge, S. C., Moore, F. A., Mercier, N. R., Cox, M., Wu, Q., Moldawer, L. L., Mohr, A. M., Efron, P. A., & Smith, S. R. (2019) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2019.04.014 · Cited by 46 · see citing works
Intra-islet glucagon-like peptide 1
Fava, G. E., Dong, E. W., & Wu, H. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.05.016 · Cited by 45 · see citing works
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
Gutierrez, A. D., Gao, Z., Hamidi, V., Zhu, L., Saint Andre, K. B., Riggs, K., Ruscheinsky, M., Wang, H., Yu, Y., Miller, C., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100813 · Cited by 44 · see citing works
Knudsen, J. G., Gudiksen, A., Bertholdt, L., Overby, P., Villesen, I., Schwartz, C. L., & Pilegaard, H. (2017) · PLOS ONE · doi:10.1371/journal.pone.0189301 · Cited by 42 · see citing works
Yasrebi, A., Rivera, J. A., Krumm, E. A., Yang, J. A., & Roepke, T. A. (2017) · Endocrinology · doi:10.1210/en.2016-1535 · Cited by 40 · see citing works
Knudsen, S. H., & Pedersen, B. K. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0642-1 · Cited by 41 · see citing works
Maximizing Longevity and Healthspan: Multiple Approaches All Converging on Autophagy
Bareja, A., Lee, D. E., & White, J. P. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00183 · Cited by 41 · see citing works
Agarwal, P., Brar, N., Morriseau, T. S., Kereliuk, S. M., Fonseca, M. A., Cole, L. K., Jha, A., Xiang, B., Hunt, K. L., Seshadri, N., et al. (2019) · Endocrinology · doi:10.1210/en.2019-00232 · Cited by 34 · see citing works
- Authors
- Ellingsgaard, H., Hauselmann, I., Schuler, B., Habib, A. M., Baggio, L. L., Meier, D. T., Eppler, E., Bouzakri, K., Wueest, S., Muller, Y. D., Hansen, A. M. K., Reinecke, M., Konrad, D., Gassmann, M., Reimann, F., Halban, P. A., Gromada, J., Drucker, D. J., Gribble, F. M., Ehses, J. A., & Donath, M. Y.
- Affiliations
- University Hospital of Basel (CH)
- University of Zurich (CH)
- Addenbrooke's Hospital (GB)
- Lunenfeld-Tanenbaum Research Institute (CA)
- University of Geneva (CH)
- Novo Nordisk (Denmark) (DK)
- University of British Columbia (CA)
- Corresponding author
- Ellingsgaard, Helga
- ORCID
- Venue
- Nature Medicine
- Published
- 2011-10-30
- Volume
- 17
- Issue
- 11
- Pages
- 1481-1489
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4286294
- OpenAlex
- W2134285290
- Cited by
- 922
- References
- 0
- Citations by year
- 2026: 33 · 2025: 56 · 2024: 80 · 2023: 59 · 2022: 70 · 2021: 62 · 2020: 55 · 2019: 79 · 2018: 65 · 2017: 69 · 2016: 69 · 2015: 50 · 2014: 69 · 2013: 63 · 2012: 42
- FWCI
- 56.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- HAL (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (WT088357, #WT084210, 088357, 084210)
- Canadian Institutes of Health Research (93749)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- interleukin-6, glucagon-like peptide-1, insulin secretion, L cells, alpha cells, proglucagon, prohormone convertase 1/3, physical activity, type 2 diabetes, glycemic control, incretins, IL-6 neutralization
- MeSH terms
- Insulin Secretion, Interleukin-6 Inhibitors, Animals, Blood Glucose, Cells, Cultured, Diabetes Mellitus, Type 2, Disease Models, Animal, Female, Glucose Tolerance Test, Humans, Insulin, Male, Mice, Inbred C57BL, Mice, Transgenic, Physical Conditioning, Animal, Signal Transduction, Interleukin-6, Enteroendocrine Cells, Glucagon-Secreting Cells, Mice, Glucagon-Like Peptide 1, Diet, High-Fat
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