Relative Contribution of Brain Insulin Action for Postprandial Metabolism
概览
- 阶段
- 不适用
- 干预措施
- Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray
- 疾病 / 适应症
- Glucose Metabolism Disorders
- 发起方
- University of Ulm
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Endogenous glucose production
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women.
Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.
详细描述
This research project aims to investigate to what extent brain insulin action is responsible for the control of postprandial metabolism compared to direct effects of insulin in peripheral target tissues. Furthermore, the study will investigate sex differences and the influence of the menstrual cycle on brain-derived coordination of postprandial signaling for metabolic control. Therefore, insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 15 minutes before a 75 gram oral glucose tolerance test that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. This approach will be combined with a double-tracer dilution technique. Labeled glucose (\[6,6-2H\]glucose) will be infused 120 minutes before and during the OGTT (180 min) and will be used to address endogenous glucose production. The glucose drink from the OGTT will be enriched with \[U-13C6\]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd). Using this approach, brain-derived regulation of postprandial metabolism including endogenous glucose production, glucose disappearance, insulin secretion, and secretion of proglucagon-cleavage products (incretins) will be examined.
研究者
Martin Heni
Prof. Dr. med. Martin Heni
University of Ulm
入排标准
入选标准
- •BMI \< 24 kg/m2
- •no known primary diseases
- •no hormonal contraception
排除标准
- •Alcohol or drug abuse
- •At screening: Hb \< 12 g/dl for women and Hb \< 14 g/dl for men
- •Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.
研究组 & 干预措施
Intranasal insulin spray
160 Units of human insulin as nasal spray
干预措施: Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray
Placebo spray
Nasal spray containing placebo solution
干预措施: Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray
结局指标
主要结局
Endogenous glucose production
时间窗: -120 minutes - 180 minutes during oral glucose tolerance test
Effect of intranasal insulin versus placebo on endogenous glucose production assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
Rate of glucose disappearance
时间窗: -120 minutes - 180 minutes during oral glucose tolerance test
Effect of intranasal insulin versus placebo on rate of glucose disappearance (Rd) assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
次要结局
- Post-absorptive energy expenditure(30 minutes and 180 minutes during oral glucose tolerance test)
- Sex differences(-120 minutes - 180 minutes during oral glucose tolerance test)
- Autonomic nervous system activity(-15 minutes - 180 minutes during oral glucose tolerance test)
- Glucose tolerance(0-120 minutes during oral glucose tolerance test)
- Whole-body insulin sensitivity(0-120 minutes during oral glucose tolerance test)
- Proglucagon cleavage products(0-120 minutes during oral glucose tolerance test)
- Insulin secretion(0-180 minutes during oral glucose tolerance test)
- Menstrual cycle effects(-120 minutes - 180 minutes during oral glucose tolerance test)