The Role of Genetic Variation in CLTCL1 and Other Related Genes in Relation to Whole-body Glucose Control: A Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 2
- 主要终点
- Peak plasma glucose (CHC22 genotype)
研究概览
简要总结
Maintaining stable blood glucose concentrations after eating has important implications for health. Individuals who are better able to maintain stable blood glucose concentrations after consuming carbohydrate have a lower risk of mortality from cardiovascular disease. Muscle is the primary tissue for glucose disposal following a meal, and responsiveness of this tissue to insulin is dictated by GLUT4 translocation to the muscle cell membrane. Clathrin heavy chain isoform 22 (CHC22) is a protein that plays a key role in intracellular GLUT4 action, and it may play an important role in whole-body glucose control. Genetic variation in the gene which codes for CHC22 may be able to explain differences in glucose control at the whole-body level.
详细描述
The ability to maintain relatively stable blood glucose concentrations after eating has important implications for health. Individuals who are better able to maintain stable blood glucose concentrations after consuming carbohydrate have a lower risk of mortality and morbidity from cardiovascular disease. Muscle is the primary tissue for glucose disposal after a meal and the ability to tolerate a glucose load is largely dependent on the ability of muscle to respond to insulin by translocating the glucose transporter, GLUT4, to the muscle cell membrane, facilitating glucose import into muscle from the circulation. Therefore, by understanding the mechanisms that explain why some people are better able to maintain glucose control can give insight into how to target physiological pathways (such as muscle glucose uptake) to reduce disease risk and improve health.
Clathrins are cytoplasmic proteins that play essential roles in cell membrane trafficking pathways. Pilot data indicate that the clathrin heavy chain isoform 22 (CHC22) plays a key role in intracellular targeting of GLUT4 and may therefore play an important role in whole-body glucose control. Cell-based studies suggest that genetic variation in the CLTCL1 gene (which encodes for CHC22) at SNP rs1061325, influences GLUT4 retention. It is currently unknown whether genetic variation in CHC22 has consequences for whole-body glucose control in humans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index between 18.5-29.9 kg/m^2
- •Aged 18-65 years
- •Able and willing to provide informed consent and safely comply with study procedures
排除标准
- •Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias
- •Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes)
- •Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
- •Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)
结局指标
主要结局
Peak plasma glucose (CHC22 genotype)
时间窗: 2 hours
Plasma glucose samples will be obtained throughout the 2-hour postprandial period and the peak glucose concentration will be measured, this will be grouped by CHC22 genotype.
Plasma glucose incremental area under the curve (CHC22 genotype)
时间窗: 2 hours
Plasma glucose samples will be obtained throughout the 2-hour postprandial period and the incremental area under the curve will be calculated, this will be grouped by CHC22 genotype.
次要结局
- Plasma glucose incremental area under the curve (other genotypes)(2 hours)
- Fasting plasma glucose concentrations (CHC22 genotype)(2 hours)
- Fasting plasma glucose concentrations (other genotypes)(2 hours)
- Matsuda insulin sensitivity index(2 hours)
- Homeostasis model of insulin resistance(2 hours)
研究者
Javier Gonzalez
Senior Lecturer
University of Bath