Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control
Louise Lang Lehrskov, Mark Preben Lyngbaek, Line Soederlund, Grit Elster Legaard, Jan Adam Ehses, Sarah Elizabeth Heywood, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst, Kristian Karstoft, Bente Klarlund Pedersen, Helga Ellingsgaard, Louise Lang Lehrskov, Mark Preben Lyngbaek, Line Soederlund, Grit Elster Legaard, Jan Adam Ehses, Sarah Elizabeth Heywood, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst, Kristian Karstoft, Bente Klarlund Pedersen, Helga Ellingsgaard
Abstract
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: exercise; gastric emptying; glucagon; glucagon-like peptide-1; glucose homeostasis; inflammation; insulin; interleukin-6; type 2 diabetes.
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Source: PubMed