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

NCT ID: NCT03660332

Last Updated: 2024-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-01
• Study Completion Date: 2017-04-01

Brief Summary

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 Data showed that this delay in GE is associated with much improved glucose tolerance and insulin secretion (unpublished data).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.

Conditions

Postprandial Glucose Homeostasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

IL-6 infusion

Healthy young men will receive IL-6 infusion

Group Type: ACTIVE_COMPARATOR

Infusion of a liquid meal intraduodenally

Intervention Type: PROCEDURE

Infusion of IL-6/NaCL before a liquid meal intraduodenally

Placebo infusion

Healthy young men will receive saline infusion

Group Type: PLACEBO_COMPARATOR

Infusion of a liquid meal intraduodenally

Intervention Type: PROCEDURE

Infusion of IL-6/NaCL before a liquid meal intraduodenally

Interventions

Infusion of a liquid meal intraduodenally

Infusion of IL-6/NaCL before a liquid meal intraduodenally

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Louise Lang Lehrskov

MD, PhD student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bente K Pedersen, Professor

Role: STUDY_DIRECTOR

CFAS, Rigshospitalet

Locations

Rigshospitalet, Centre of Inflammation and Metabolism (CIM) Centre for Physical Activity Research (CFAS)

Copenhagen, , Denmark

Countries

Denmark

References

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.

Reference Type: RESULT

PMID: 29731416 (View on PubMed)

Other Identifiers

H-16036538

Identifier Type: -

Identifier Source: org_study_id