Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control

TY - JOUR

T1 - Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control

AU - Lehrskov, Louise Lang

AU - Lyngbaek, Mark Preben

AU - Soederlund, Line

AU - Legaard, Grit Elster

AU - Ehses, Jan Adam

AU - Heywood, Sarah Elizabeth

AU - Albrechtsen, Nicolai Jacob Wewer

AU - Holst, Jens Juul

AU - Karstoft, Kristian

AU - Pedersen, Bente Klarlund

AU - Ellingsgaard, Helga

PY - 2018/6/5

Y1 - 2018/6/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.cmet.2018.04.008

DO - 10.1016/j.cmet.2018.04.008

M3 - Journal article

C2 - 29731416

SN - 1550-4131

VL - 27

SP - 1201

EP - 1211

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -