Syntaxin phosphorylation and GLUT4 sorting in human muscle
Research type
Research Study
Full title
Syntaxin phosphorylation as an insulin-regulatory node of GLUT4 sorting in human muscle
IRAS ID
224766
Contact name
James Boyle
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Current therapies for Type 2 diabetes (T2DM) are “one size fits all” rather than addressing the specific aspects of metabolism affected by the condition. Individuals with insulin-resistance and T2DM exhibit a significant impairment in the ability of insulin to stimulate glucose transport. Our project focuses on these molecular abnormalities that underlie GLUT4 storage and trafficking, and how these relate to insulin resistance and ultimately T2DM. This may lead to more targeted ‘Precision Medicine’ approaches or potentially to the discovery of more widely applicable drug targets. \nThis study involves participants with type 2 diabetes as well as age and BMI matched controls. The participants will undergo baseline investigations, including blood pressure, BMI measurements and routine blood testing. We will perform an oral glucose tolerance test on the control participants to ensure they do not have underlying and undiagnosed diabetes or impaired glucose tolerance. Following this, all participants will undergo a baseline muscle biopsy in the fasted state from the vastus lateralis in the quadriceps muscle. Thereafter, we will perform an insulin suppression test which involves simultaneous infusions of insulin, dextrose and octreotide to allow us to calculate the individuals level of insulin sensitivity. This insulin suppression test lasts for 3 hours, with blood testing every 30 minutes, and during which time the muscle biopsy is repeated. By repeating the muscle biopsy, this allows us to compare the fasted and insulin stimulated muscle. \nThese specimens will then be snap frozen in liquid nitrogen and transported to Professor Gould’s laboratory where we will perform a variety of laboratory techniques, including quantitative immunoblotting to identify differences in the levels of key proteins between the fasted and insulin stimulated states, as well as between controls and participants with type 2 diabetes.\n\n
REC name
West of Scotland REC 1
REC reference
17/WS/0214
Date of REC Opinion
20 Dec 2017
REC opinion
Further Information Favourable Opinion