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

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 Data showed that this delay in GE is associated with much improved glucose tolerance and insulin secretion (unpublished data).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

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

Conditions
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Postprandial Glucose Homeostasis

Intervention / Treatment
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* Procedure: Infusion of a liquid meal intraduodenally


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |