Studies of Insulin and Glucagon Action in the Liver
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Glucose appearance (Ra)
研究概览
简要总结
This study examines how glucagon works to regulate glucose metabolism, based on new findings that suggest glucagon signaling in the liver has more than one role, and that these multiple roles can be opposing in nature. Understanding this biology provides an opportunity to develop new generations of glucagon-based drugs that target specific pathways, making them more effective at controlling blood glucose.
Participants will complete paired, 5-hour hyperinsulinemic glucose clamp visits in which they receive either glucagon or saline infusions while blood glucose is maintained and frequent blood samples are collected. The primary focus is whether coordinated glucagon and insulin signaling enhances hepatic insulin sensitivity.
详细描述
Volunteers will undergo screening for medical history, medication usage, and blood work; those who qualify will be offered participation. Study participation will last approximately 5-12 weeks depending on appointment availability and the number of infusions planned. This protocol involves two sets of paired procedures. Approximately 15 participants will complete each set of paired visits. Participants can opt to complete one set of paired visits or both sets of paired visits.
Set 1: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of glucagon on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a stepwise glucagon infusion will be administered.
Set 2: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of insulin on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a steady glucagon infusion will be administered.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults age 18-45 years
- •Body Mass Index (BMI) < 27.0 kg/m²
- •Fasting plasma glucose ≤ 95 mg/dL or HbA1c ≤ 5.8% as measured at screening visit
排除标准
- •Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders
- •No personal history of diabetes or pancreatitis
- •No personal history of cardiac, gastrointestinal, renal or liver disease
- •No history of diabetes among any first-degree family members
- •Renal insufficiency (eGFR < 60 mL/kg/min)
- •Anemia (hematocrit < 34%) as measured at screening visit
- •Pregnant females
- •Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
研究组 & 干预措施
Saline infusion during hyperinsulinemic clamp
Saline infusion during the final 90 minutes of an otherwise identical clamp procedure.
干预措施: Saline (placebo) (Drug)
Glucagon infusion during hyperinsulinemic clamp
Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols.
干预措施: Glucagon (Drug)
结局指标
主要结局
Glucose appearance (Ra)
时间窗: In these experiments outcomes will be based on measurements made in the final 90 minutes of the hyperinsulinemic glucose clamp.
Glucose appearance will be determined using steady state computations, unless a stable tracer:tracee ratio is not maintained
Glucose disappearance (Rd)
时间窗: In the experiments described here glucose turnover (Ra and Rd) will be determined in the final 90 minutes of the hyperinsulinemic glucose clamp.
Glucose disappearance (Rd) will be determined using steady state computations, unless a stable tracer:tracee ratio is not maintained
Hepatic insulin sensitivity
时间窗: Basal period (time -30-0 min), after the insulin infusion alone (60-90 min), and during the glucagon/saline infusions (120-180 min)
Hepatic insulin sensitivity will be calculated as EGP divided by insulin concentration
次要结局
未报告次要终点