The Role of ATGL and G0/G1 Switch Gene Complex in Lipopolysaccaride (LPS) Induced Ketosis - a Controlled, Randomised, Clinical Experimental Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Insulin signaling expressed as a CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue.
研究概览
简要总结
Hypothesis
- To define whether stimulation of ATGL and suppression of G0/G1 switch gene occur in the initial phases of diabetic ketoacidosis and thus can be identified as the primary mechanisms behind this life threatening condition.
- Make a human model for studying ketoacidosis.
The investigators plan to reduce in their regular insulin over night. In the morning we administer endotoxin, which together with a relative lack of insulin will initiate ketogenesis - a state of ketoacidosis. On another occasion strict glycemic control is imposed by means of intravenous insulin. The testing is done two separate days with at least 3 weeks in between and patients are admitted to hospital the evening before the day of testing. The investigators use isotopic tracers to determine metabolic fluxes and analyse fat (ATGL, G0/G1 switch gene) and muscle biopsies.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Diabetes type 1
- •19 < BMI < 26
- •minimal or negative C-peptide
- •written consent
排除标准
- •Severe comorbidity
- •regular medication apart from insulin
结局指标
主要结局
Insulin signaling expressed as a CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue.
时间窗: Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 (-75min) am t2=11.15 (195min) am t3= 12.30 pm (270min)
Change in phosphorylation of target proteins and messenger RNA (mRNA) expression of target genes assessed with western blotting technique.
次要结局
- Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies(Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 am (-75min) t2=11.15 (195min) am t3= 12.30 pm (270min))
- Metabolism(Change in glucose, fat and protein metabolism between study days and during each study day)
- Cytokines and stress hormones(In basal period t=0-240 minutes and in clamp period t=240-390 minutes)