Glucose Control
Conditions
Keywords
Glucose, Genetic variation, CHC22, CLTCL1
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTOral glucose tolerance test
Participants will ingest 75 g anhydrous glucose dissolved in water and the blood responses will be measured over the following 2-hours using a venous cannula.
Sponsors
University College, London
Javier Gonzalez
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma glucose incremental area under the curve (CHC22 genotype) | 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. |
| Peak plasma glucose (CHC22 genotype) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting plasma glucose concentrations (other genotypes) | 2 hours | Plasma glucose will be measured at baseline and will be grouped by genotypes related to glucose control and sweet taste sensitivity. |
| Fasting plasma glucose concentrations (CHC22 genotype) | 2 hours | Plasma glucose will be measured at baseline and will be grouped by CHC22 genotype. |
| Homeostasis model of insulin resistance | 2 hours | Homeostasis model of insulin resistance will be calculated using blood samples collected in the 2-hour postprandial period. |
| Matsuda insulin sensitivity index | 2 hours | Matsuda insulin sensitivity index will be calculated using blood samples collected in the 2-hour postprandial period. |
| Plasma glucose incremental area under the curve (other genotypes) | 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 genotyping other genes related to glucose control or sweet taste sensitivity. |
Countries
United Kingdom
Outcome results
None listed