The Effects of Glucagon on Hepatic Metabolism
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Adrian Vella
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Rate of Amino acid catabolism in the presence / absence of glucagon
研究概览
简要总结
Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).
详细描述
T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing EGP. Although these effects are magnified by decreased and delayed insulin secretion, they are also apparent when insulin secretion is intact. In rodents, altered glucagon signaling changes α-cell function and mass - an effect mediated by changes in circulating AA concentrations. Are the elevated concentrations of branched-chain AA and other AA metabolites in T2DM a cause or an effect of global α-cell dysfunction? Could altered glucagon signaling precipitate a vicious cycle resulting in T2DM?
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing to participate
- •Able to give consent
排除标准
- •History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy.
- •Active systemic illness or malignancy.
- •Symptomatic macrovascular or microvascular disease.
- •Contraindications to MRI (e.g. metal implants, claustrophobia).
- •Hematocrit < 35%
- •TSH < 0.4 or > 5.
- •Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire
研究组 & 干预措施
Healthy Adults
We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.
干预措施: Glucagon response study (Drug)
Obese Adults
We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.
干预措施: Glucagon response study (Drug)
Adults with Type 2 Diabetes
We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.
干预措施: Glucagon response study (Drug)
结局指标
主要结局
Rate of Amino acid catabolism in the presence / absence of glucagon
时间窗: 240 minutes of study
Tracer-dependent measurement of amino-acid clearance
次要结局
- Effect of Diabetes on amino-acid catabolism(240 minutes of study)