Abstract

Interleukin 6 (IL‐6) is a cytokine secreted from skeletal muscle in response to exercise which, based on animal and cell studies, has been suggested to contribute to glucose metabolism by increasing secretion of the incretin hormone glucagon‐like peptide‐1 (GLP‐1) and affecting secretion of insulin and glucagon from the pancreatic islets. We investigated the effect of IL‐6 on GLP‐1 secretion in GLP‐1 producing cells (GLUTag) and using the perfused mouse small intestine (harboring GLP‐1 producing cells). Furthermore, the direct effect of IL‐6 on insulin and glucagon secretion was studied using isolated perfused mouse pancreas. Incubating GLUTag cells with 1000 ng/mL of IL‐6 for 2 h did not significantly increase secretion of GLP‐1 whereas 10 mmol/L glucose (positive control) did. Similarly, IL‐6 (100 ng/mL) had no effect on GLP‐1 secretion from perfused mouse small intestine whereas bombesin (positive control) increased secretion. Finally, administering IL‐6 (100 ng/mL) to perfused mouse pancreases did not significantly increase insulin or glucagon secretion regardless of perfusate glucose levels (3.5 vs. 12 mmol/L glucose). Acute effects of IL‐6 therefore do not seem to include a stimulatory effect on GLP‐1 secretion in mice.

Highlights

  • Interleukin-6 (IL-6) is a cytokine, secreted from immune cells and other cells, which has both pro-inflammatory and anti-inflammatory effects (Fischer 2006; Scheller et al 2011)

  • To address whether elevated circulating IL-6 has an impact on enteroendocrine glucagon-like peptide1 (GLP-1) secretion, we infused recombinant IL-6 protein (100 ng/mL) into the arterial supply of the in situ perfused proximal mouse small intestine a 2018 The Authors

  • To verify that the IL-6 which was infused in these experiments was still bioactive during the perfusion, we used the phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) as a bioassay, by incubating mouse B-lymphocytic A20 cells with perfusion effluents from same experiments as shown in Figure 1A and B

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Summary

Introduction

Interleukin-6 (IL-6) is a cytokine, secreted from immune cells and other cells, which has both pro-inflammatory and anti-inflammatory effects (Fischer 2006; Scheller et al 2011). The role of IL-6 in regulation of glucose metabolism is not well-characterized (Xu et al 2003; Fischer 2006; Ellingsgaard et al 2008; Timper et al 2016) Conflicting evidence regarding both harmful and beneficial effects of IL-6 have been reported: in humans, adipose tissue derived IL-6 was found to contribute to insulin resistance in type 2 diabetes, whereas skeletal muscle derived IL-6, secreted in response to an acute bout of exercise, may be associated with improved beta-cell function and insulin sensitivity (Ostrowski et al 1998; Steensberg et al 2000; Carey et al 2006). GLP-1 is normally secreted from L-cells in response to nutrient ingestion and binds to its cognate receptor expressed on pancreatic beta-cells,

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