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 -
