None listed
Conditions
Brief summary
After consuming a meal, blood glucose levels rise which results in the pancreas secreting the hormone insulin. Insulin increases blood flow in skeletal muscle (similar to exercise) and this blood flow effect helps deliver the glucose to the muscle for storage (1, 2). We have recently shown that if someone consumes only glucose in their meal this results in an impairment in muscle blood flow (3). We have recently built on this finding to show that when matched for blood glucose levels, intravenously infused glucose (which by-passes the gut) has the opposite effect and stimulates muscle blood flow (not published). Therefore, our data suggests that a gut-derived factor could be regulating the impaired muscle blood flow observed with orally ingested glucose. The aim of this project is to investigate the effects of one of these gut-hormones called Gastric Inhibitory Polypeptide (GIP) on muscle blood flow. Findings from this study will enhance our knowledge and understanding of blood flow regulation after a meal and has implications in the consumption of high glycemic-index food and drinks. References: 1. Clark MG, Wallis MG, Barrett EJ, Vincent MA, Richards SM, Clerk LH, et al. Blood flow and muscle metabolism: a focus on insulin action. American Journal of Physiology-Endocrinology And Metabolism. 2003;284(2):E241-E58. 2. Keske MA, Dwyer RM, Russell RD, Blackwood SJ, Brown AA, Hu D, et al. Regulation of microvascular flow and metabolism: An overview. Clinical and Experimental Pharmacology and Physiology. 2017;44(1):143-9. 3. Russell RD, Hu D, Greenaway T, Sharman JE, Rattigan S, Richards SM, et al. Oral Glucose Challenge Impairs Skeletal Muscle Microvascular Blood Flow in Healthy People. American Journal of Physiology-Endocrinology and Metabolism. 2018.
Interventions
This study is a cross-over trial comparing the effect of gastric inhibitory polypeptide (GIP) versus saline on skeletal muscle blood flow. Each participant will receive both treatments (intravenous infusions) in the following order: Infusions: 1) GIP - infused intravenously at 2 pmol/kg/min for 120 mins to raise plasma GIP levels. 2) Saline - infused intravenously for 120 mins. A total of 13 healthy individuals with no history of cardiometabolic disease will be required to complete the study. Participants will be invited to attend an initial screening/familiarisation session, followed by 2 clinical testing sessions between 1 and 4 weeks apart. Participants will receive the GIP infusion first and then crossed-over to the saline infusion on the second clinical testing visit. In addition to GIP and saline infusion, all participants will also undergo a variable rate intravenous glucose tolerance test to mimic blood glucose excursions similar to an oral glucose tolerance test. The following measurements will be conducted: Clinical chemistries and anthropometrics: Fasting clinical chemistries (glucose, insulin, lipid profile, HbA1c) and body composition (height, weight) will be measured. Clinical chemistries will be assessed via an accredited pathology laboratory. Microvascular blood flow responses in skeletal muscle: Microvascular blood flow will be measured via contrast-enhanced ultrasound imaging of the thigh muscle at baseline (0 min) and at 60 min and 120 min post-GIP and -saline infusion. Femoral artery blood flow responses: Femoral artery blood flow will be measured via 2D and Doppler ultrasound imaging at baseline (0 min) and at 60 min and 120 min post-GIP and -saline infusion. Metabolic and hormonal responses: Blood glucose, plasma insulin and plasma GIP levels will be measured at regular time points over 120 mins during the infusion of GIP and saline.
Sponsors
Study design
Eligibility
Inclusion criteria
1. Aged 18-50 years 2. Body mass index (BMI) range 18.5-30kg/m2 3. Normotensive (seated brachial blood pressure <140/90 mmHg) 4. Provided signed informed consent to participate in the study
Exclusion criteria
1. Aged <18 >50 years 2. BMI range <18.5 >30kg/m2 3. Brachial blood pressure >140/90 mm/Hg, or taking an anti-hypertensive for elevated blood pressure. 4. A first degree relative (eg. parent) with diagnosed Type 2 diabetes 5. >1 grandparent with diagnosed Type 2 diabetes 6. Personal history of any of the following: - Diabetes - Myocardial infarction (MI) - Cardiovascular disease - Stroke - Peripheral artery disease - Pulmonary disease - Arthritis muscular skeletal disease - Liver disease 7. Malignancy within the past 5 years 8. Current smoker 9. Pregnancy/ lactation 10. Women with an irregular menstrual cycle