Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells

By H. Ellingsgaard, Irina Hauselmann, Beat Schuler, A. Habib, L. Baggio, Daniel T. Meier, E. Eppler, K. Bouzakri, S. Wueest, Y. Muller and 11 more. Nature Medicine, 2011

882 citations recorded by the source corpus.

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.

Subfields: Endocrine and Autonomic Systems, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/fa810f490a6b57b7f146873fb53fc1e8380e4ed2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. D. J. Drucker
2. B. K. Pedersen
3. Matthias Tschöp

In Epidemiology

1. M. C. Severinsen
2. B. K. Pedersen
3. Haiming Cao

In Physiology

1. M. C. Severinsen
2. J. Zierath
3. B. Egan
4. B. K. Pedersen
5. Matthias Tschöp
6. Haiming Cao

Citations in the corpus

• Pharmacology, physiology, and mechanisms of incretin hormone action. (2013, background): “GLP-1 production in rodent and human a cells is induced by interleukin-6 (IL-6), as exemplified by exercise or exogenous administration of IL-6 (Ellingsgaard et al., 2011).”
• Exercise metabolism and the molecular regulation of skeletal muscle adaptation. (2013, background): “For instance, IL-6 is a cytokine that can regulate glycemia directly by stimulating glucose uptake in skeletal muscle (Glund et al., 2007), and indirectly by acting on L cells in the intestine and a cells in the pancreas to improve b cell function and insulin secretion (Ellingsgaard et al., 2011).”
• Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020, background): “Other rodent studies show that IL-6 triggers proliferation of pancreatic alpha cells in the obese state (108) and stimulates the production of glucagon-like peptide (GLP)-1 and hence insulin secretion (108).”
• Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines (2013, neutral): “recently shown to stimulate insulin secretion via enhanced GLP-1 (glucagon-like peptide-1) expression in pancreatic cells [38].”
• Glucagon-like peptide 1 (GLP-1) (2019, background): “Islet GLP-1 production is also mediated by the cytokine IL-6, which is released in response to exercise, obesity and diabetes [163,164].”