Postprandial Glucose Homeostasis
Conditions
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 Data showed that this delay in GE is associated with much improved glucose tolerance and insulin secretion (unpublished data).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.
Interventions
PROCEDUREInfusion of a liquid meal intraduodenally
Infusion of IL-6/NaCL before a liquid meal intraduodenally
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The paracetamol uptake | 0-14 days | paracetamol blood levels (mmol/l) on both study days. The paracetamol absorbance will be compared between the 2 study days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GLP-1 secretion | 0-14 days | Active GLP-1 blood levels on both study days. The levels on the 2 study days will be compared. |
| Glucagon secretion | 0-14 days | Glucagon blood levels on both study days. The levels on the 2 study days will be compared. |
| Insulin levels | 0-14 | Insulin blood levels on both study days. The levels on the 2 study days will be compared. |
| Glucose | 0-14 | Plasma glucose levels on both study days. The levels on the 2 study days will be compared. |
Countries
Denmark
Outcome results
None listed