The Effect of an Acute Increase in Plasma IL-6 on Glucose Tolerance When a Meal is Administered Intraduodenally
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- The paracetamol uptake
研究概览
简要总结
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 Data showed that this delay in GE is associated with much improved glucose tolerance and insulin secretion (unpublished data).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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years and ≤ 35 years
- •Healthy (based on screening)
排除标准
- •BMI < 18 and > 25 kg/m2
- •Evidence of severe thyroid, liver, lung, heart or kidney disease
结局指标
主要结局
The paracetamol uptake
时间窗: 0-14 days
paracetamol blood levels (mmol/l) on both study days. The paracetamol absorbance will be compared between the 2 study days.
次要结局
- GLP-1 secretion(0-14 days)
- Insulin levels(0-14)
- Glucose(0-14)
- Glucagon secretion(0-14 days)
研究者
Louise Lang Lehrskov
MD, PhD student
Rigshospitalet, Denmark