The Effect of an Acute Increase in Plasma IL-6 on Glucose Tolerance When a Meal is Administered Intraduodenally (DUIL-6)

The aim of the study is to investigate and clarify whether the effect of IL-6 on glucose tolerance and insulin secretion are secondary to the changes in gastric emptying.

The literature provides no information regarding a role for interleukin-6 (IL-6) in the regulation of beta cell function (glucose or meal-stimulated insulin secretion) in humans. Previous studies infusing IL-6 into humans have primarily focused on insulin action and the effects on peripheral insulin sensitivity whereas a potential effect on insulin secretion has been neglected.

We have demonstrated that an acute increase in IL-6, obtained by a single bolus of IL-6, potentiated glucose-induced insulin secretion in a glucagon-like peptide-1 (GLP-1) dependent manner in mice1. In mice, IL-6 enhanced insulin secretion in a dose- and glucose-dependent manner, along with increasing concentrations of GLP-1. Interleukin-6 had no effect on insulin secretion in GLP-1 receptor knock-out mice or in mice treated with the GLP-1 receptor antagonist. Thus, in mice, GLP-1 has proven an essential mediator of IL-6 actions on beta cell function.

Importantly, a single bolus of IL-6 also significantly increased glucose-stimulated insulin secretion in several mouse models of obesity and diabetes (diet-induced obesity, the ob/ob and the db/db mouse).

Own data show that an infusion of IL-6 causes a significant delay in the rate of gastric emptying (GE) after a mixed meal in healthy young men. Data showed that this delay in GE is associated with much improved glucose tolerance and insulin secretion (unpublished data).

In the present study we wish to investigate whether the beneficial effects of IL-6 on postprandial glucose tolerance and insulin secretion are dependent on a delay in gastric emptying. We will bypass the ventricle and infuse a mixed meal directly into the duodenum of healthy young men.

This study has the potential to show that the known effect of IL-6 on postprandial glucose tolerance is dependent on a delayed GE.

Study Overview

• Status: Completed
• Conditions: Postprandial Glucose Homeostasis
• Intervention / Treatment: Procedure: Infusion of a liquid meal intraduodenally

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Centre of Inflammation and Metabolism (CIM) Centre for Physical Activity Research (CFAS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥ 18 years and ≤ 35 years
• Healthy (based on screening)

Exclusion Criteria:

• Smoking
• BMI < 18 and > 25 kg/m2
• Evidence of severe thyroid, liver, lung, heart or kidney disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IL-6 infusion; Healthy young men will receive IL-6 infusion	Procedure: Infusion of a liquid meal intraduodenally; Infusion of IL-6/NaCL before a liquid meal intraduodenally
Placebo Comparator: Placebo infusion; Healthy young men will receive saline infusion	Procedure: Infusion of a liquid meal intraduodenally; Infusion of IL-6/NaCL before a liquid meal intraduodenally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The paracetamol uptake	paracetamol blood levels (mmol/l) on both study days. The paracetamol absorbance will be compared between the 2 study days.	0-14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GLP-1 secretion	Active GLP-1 blood levels on both study days. The levels on the 2 study days will be compared.	0-14 days
Glucagon secretion	Glucagon blood levels on both study days. The levels on the 2 study days will be compared.	0-14 days
Insulin levels	Insulin blood levels on both study days. The levels on the 2 study days will be compared.	0-14
Glucose	Plasma glucose levels on both study days. The levels on the 2 study days will be compared.	0-14

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Bente K Pedersen, Professor, CFAS, Rigshospitalet

Publications and helpful links

General Publications

• Lang Lehrskov L, Lyngbaek MP, Soederlund L, Legaard GE, Ehses JA, Heywood SE, Wewer Albrechtsen NJ, Holst JJ, Karstoft K, Pedersen BK, Ellingsgaard H. Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control. Cell Metab. 2018 Jun 5;27(6):1201-1211.e3. doi: 10.1016/j.cmet.2018.04.008. Epub 2018 May 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: H-16036538

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No