Cell Metabolism
Volume 27, Issue 6, 5 June 2018, Pages 1201-1211.e3
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Clinical and Translational Report
Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control

https://doi.org/10.1016/j.cmet.2018.04.008Get rights and content
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Highlights

  • IL-6 delays the rate of gastric emptying in humans

  • Postprandial glycemia is reduced due to IL-6-induced delay in gastric emptying

  • IL-6 also reduces postprandial insulin secretion in humans

  • Effects of IL-6 on gastric emptying and insulin secretion are maintained in T2DM

Summary

Gastric emptying is a critical regulator of postprandial glucose and delayed gastric emptying is an important mechanism of improved glycemic control achieved by short-acting glucagon-like peptide-1 (GLP-1) analogs in clinical practice. Here we report on a novel regulatory mechanism of gastric emptying in humans. We show that increasing interleukin (IL)-6 concentrations delays gastric emptying leading to reduced postprandial glycemia. IL-6 furthermore reduces insulin secretion in a GLP-1-dependent manner while effects on gastric emptying are GLP-1 independent. Inhibitory effects of IL-6 on gastric emptying were confirmed following exercise-induced increases in IL-6. Importantly, gastric- and insulin-reducing effects were maintained in individuals with type 2 diabetes. These data have clinical implications with respect to the use of IL-6 inhibition in autoimmune/inflammatory disease, and identify a novel target that could be exploited pharmacologically to delay gastric emptying and spare insulin, which may be beneficial for the beta cell in type 2 diabetes.

Keywords

gastric emptying
interleukin-6
glucagon-like peptide-1
glucose homeostasis
type 2 diabetes
exercise
inflammation
insulin
glucagon

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These authors contributed equally

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