Assessment of the Time Course of Lipid Induced Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- intramyocellular lipid metabolites
研究概览
简要总结
This study aims to explore time-dependent effects of lipid infusion an intramyocellular lipid metabolites and the induction of impaired insulin signaling.
详细描述
Increased availability of free fatty acids impairs glucose disposal in young healthy humans. Patients with type 2 diabetes have reduced whole body glucose disposal, increased ectopic lipid deposition in skeletal muscle and the liver and impaired mitochondrial function. Recent studies suggest that lipid metabolites such as diacylglycerol (DAG), ceramides and long-chain acyl-coA represent the active mediators inducing insulin resistance. Possible targets are DAG-sensitive Proteinkinase C (PKC θ, PKC ε) which inhibit the insulin signaling cascade and ceramides which interfere with the insulin signaling cascade at Proteinkinase B/AKT. Prior studies raised controvesial evidence, thus, it is yet unclear, whether DAG or ceramides are the primary agents inducig lipid-induced insulin resistance. Therefore, the current study aims to explore the time course of the appearance of intramyocellular lipid compunds during lipid infusion in parallel assessing markers of impaired insulin action.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •non-diabetic (OGTT), no family history of diabetes, BMI<30 kg/m2, age: 20-55 years, no medication
- •For the athletes group additionally:
- •VO2max > 60ml/kg/min for males and VO2max > 45ml/kg/min for females Active in endurance-exercise activities, 3 times a week for at least 2 years Stable level of training for at least 3 months
排除标准
- •acute illness within the last 2 weeks, autoimmune diseases, renal insufficiency (creatinine> 1.5 mg/dl), cardiovascular diseases, anemia (Hb< 12g/l), donation of blood within the last 4 weeks before the study, thyroid diseases, pregnancy, smoking, night-shift working (disturbed circadian rhythm), defective coagulation or wound healing, cancer, allergy against soja products
结局指标
主要结局
intramyocellular lipid metabolites
时间窗: after 4 hours lipid infusion
Muscle biopsies are taken before, after 2.5 and 4 hours of lipid infusion
muscle glucose flux
时间窗: during lipid infusion
glycogen synthesis rate, glucose-6-phosphate
次要结局
- insulin resistance of glucose uptake and mitochondrial function(after 4 hours lipid infusion)