Metabolic Signalling in Muscle- and Adipose Tissue Following Insulin Withdrawal and Growth Hormone Injection in Type I Diabetes Mellitus, a 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
- 1
- 主要终点
- Insulin and growth hormone signalling, expressed as 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
Diabetes mellitus type I (DM I) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive.
Insulin is a potent anabolic hormone with its primary targets in the liver, the skeletal muscle-tissue and - adipose-tissue.
Severe lack of insulin leads to elevated blood glucose levels, dehydration, electrolyte derangement, ketosis and thus eventually ketoacidosis.
Insulin signalling pathways are well-known.
Growth hormone (GH) is also a potent anabolic hormone, responsible for human growth and preservation of protein during fasting. GH (in concert with lack of insulin) induces lipolysis during fasting. It is not known how GH exerts its lipolytic actions.
The aim is to define insulin and growth hormone (GH) signalling pathways in 3 different states in patients with DM I.
And to test whether ATGL-related lipolysis in adipose tissue contributes to the development of ketosis.
- Good glycemic control
- Lack of insulin (ketosis/ketoacidosis)
- Good glycemic control and GH injection
详细描述
Diabetes mellitus type I (DMI ) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive.
Insulin is a potent anabolic hormone with its primary targets in- the liver, -the skeletal muscle-tissue and - fat-tissue.
In the liver it enhances glycogenesis and inhibits glycogenolysis and gluconeogenesis.
In skeletal muscle-tissue, it enhances glucose transport into the cell, glycogenesis, glycolysis, glucose oxidation and protein synthesis.
In fat-tissue, it inhibits lipolysis and enhances lipogenesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Diabetes Mellitus Type I, C-peptide negative, 19 < BMI < 26, Written consent -
排除标准
- •Ischemic heart disease, Cardiac arrythmia, Epilepsy, Other medical illness
研究组 & 干预措施
Insulin withdrawal
10 % of the individual subject's regular insulin dosage will be given as a continuous IV administration of insuman rapid overnight (hospitalized and fasting from 10 p.m.) Basal period from 7.00 am to 12.00 pm (without insulin). The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm.
Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given.
干预措施: Insulin withdrawal (Drug)
Norditropin (Growth Hormone)
Same amount of insulin administered on the control day (good glycemic control) overnight and on the study day (hospitalized and fasting from 10 p.m.). On the study day, a bolus injection of 0,4 mg of growth hormone (Norditropin) will be administered at 7.05 am. Basal period from 7.00 am to 12.00 pm (good glycemic control).The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm.
Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given.
干预措施: Norditropin (Drug)
结局指标
主要结局
Insulin and growth hormone signalling, expressed as 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= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min)
Change in phosphorylation of target proteins and mRNA (messenger RNA) 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= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min))
- Metabolism(Change in glucose, fat and protein metabolism between study days.)
- Ghrelin(Plasma samples obtained at t=0, t=15, t=30, t=45, t=60, t=75, t=90, t=105, t=120, t=150, t=180, t=210, t=240, t=270, t=300)
研究者
Thomas Schmidt Voss
MD
University of Aarhus