Universität zu Köln

Ellingsgaard, Helga, Seelig, Eleonora, Timper, Katharina, Coslovsky, Michael, Soederlund, Line, Lyngbaek, Mark P., Albrechtsen, Nicolai J. Wewer, Schmidt-Trucksass, Arno ORCID: 0000-0002-4662-3911, Hanssen, Henner, Frey, Walter O., Karstoft, Kristian, Pedersen, Bente K., Boni-Schnetzler, Marianne and Donath, Marc Y. (2020). GLP-1 secretion is regulated by IL-6 signalling: a randomised, placebo-controlled study. Diabetologia, 63 (2). S. 362 - 374. NEW YORK: SPRINGER. ISSN 1432-0428

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Abstract

Aims/hypothesis IL-6 is a cytokine with various effects on metabolism. In mice, IL-6 improved beta cell function and glucose homeostasis via upregulation of glucagon-like peptide 1 (GLP-1), and IL-6 release from muscle during exercise potentiated this beneficial increase in GLP-1. This study aimed to identify whether exercise-induced IL-6 has a similar effect in humans. Methods In a multicentre, double-blind clinical trial, we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) 8 mg/kg every 4 weeks, oral sitagliptin (a dipeptidyl peptidase-4 inhibitor) 100 mg daily or double placebos (a placebo saline infusion every 4 weeks and a placebo pill once daily) during a 12 week training intervention. The primary endpoints were the difference in change of active GLP-1 response to an acute exercise bout and change in the AUC for the concentration-time curve of active GLP-1 during mixed meal tolerance tests at baseline and after the training intervention. Results Nineteen patients were allocated to tocilizumab, 17 to sitagliptin and 16 to placebos. During the acute exercise bout active GLP-1 levels were 26% lower with tocilizumab (multiplicative effect: 0.74 [95% CI 0.56, 0.98], p = 0.034) and 53% higher with sitagliptin (1.53 [1.15, 2.03], p = 0.004) compared with placebo. After the 12 week training intervention, the active GLP-1 AUC with sitagliptin was about twofold that with placebo (2.03 [1.56, 2.62]; p < 0.001), while GLP-1 AUC values showed a small non-significant decrease of 13% at 4 weeks after the last tocilizumab infusion (0.87 [0.67, 1.12]; p = 0.261). Conclusions/interpretation IL-6 is implicated in the regulation of GLP-1 in humans. IL-6 receptor blockade lowered active GLP-1 levels in response to a meal and an acute exercise bout in a reversible manner, without lasting effects beyond IL-6 receptor blockade. Funding Danish National Research Foundation. Danish Council for Independent Research. Novo Nordisk Foundation. Danish Centre for Strategic Research in Type 2 Diabetes. European Foundation for the Study of Diabetes. Swiss National Research Foundation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ellingsgaard, Helga UNSPECIFIED UNSPECIFIED UNSPECIFIED Seelig, Eleonora UNSPECIFIED UNSPECIFIED UNSPECIFIED Timper, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Coslovsky, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Soederlund, Line UNSPECIFIED UNSPECIFIED UNSPECIFIED Lyngbaek, Mark P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Albrechtsen, Nicolai J. Wewer UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Trucksass, Arno UNSPECIFIED orcid.org/0000-0002-4662-3911 UNSPECIFIED Hanssen, Henner UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Walter O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Karstoft, Kristian UNSPECIFIED UNSPECIFIED UNSPECIFIED Pedersen, Bente K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boni-Schnetzler, Marianne UNSPECIFIED UNSPECIFIED UNSPECIFIED Donath, Marc Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124837
DOI:	10.1007/s00125-019-05045-y
Journal or Publication Title:	Diabetologia
Volume:	63
Number:	2
Page Range:	S. 362 - 374
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0428
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GLUCAGON-LIKE PEPTIDE-1; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; GLYCEMIC CONTROL; HEALTHY-SUBJECTS; PLASMA-GLUCOSE; DOUBLE-BLIND; EXERCISE; INTERLEUKIN-6 Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12483