Insulin Modulation of fMRI Connectivity and Food Reward
Overview
- Phase
- Early Phase 1
- Intervention
- Insulin
- Conditions
- Healthy Volunteers
- Sponsor
- University of Pittsburgh
- Locations
- 1
- Primary Endpoint
- fMRI BOLD Response in Brain
- Status
- Withdrawn
- Last Updated
- 8 years ago
Overview
Brief Summary
This study evaluates the effects of changing insulin levels on brain activity. Participants will complete functional magnetic resonance imaging (fMRI) scans during fasting conditions, then during an insulin infusion.
Detailed Description
Insulin is a hormone released by the pancreas in response to increases in glucose levels that result from food intake. In addition to stimulating glucose uptake in the periphery, insulin signals the central nervous system to induce satiety and inhibit feeding behavior. To begin to identify the specific effects of circulating insulin on brain networks, the current study will recruit healthy participants who will undergo two functional magnetic resonance imaging scans. One scan will be performed in the fasted state, and the alternate scan will be conducted during an isoglycemic hyperinsulinemic clamp. This project will allow us to identify the specific effects of circulating insulin on brain reactivity to palatable food.
Investigators
John Patrick Ryan
PhD
University of Pittsburgh
Eligibility Criteria
Inclusion Criteria
- •Body mass index between 18 and 24
- •HOMA-IR \< 1.55 (homeostatic model assessment of insulin resistance - ((glucose x insulin) / 405)).
Exclusion Criteria
- •Current or lifetime history of any cardiovascular disease or surgery (including hypertension, stroke, myocardial infarction, congestive heart failure, atrial or ventricular arrhythmias, coronary bypass, carotid artery, or peripheral vascular surgery)
- •Current or lifetime history of cancer, a chronic kidney or liver condition, type I or II diabetes, or any pulmonary or respiratory disease
- •Current or lifetime diagnoses of any substance abuse
- •Positive urine drug screen
- •Current or lifetime use of glucocorticoid medications for \>1 month
- •A previous cerebrovascular accident or trauma involving loss of consciousness
- •Previous neurosurgery or history of a neurological condition
- •Pregnancy (females)
- •Claustrophobia
- •Ferrous metallic implants or any surgically placed medical device not cleared for safety at 3Tesla MRI strength
Arms & Interventions
Hyperinsulinemic Clamp
Participants will complete two MRI scans approximately one hour apart - one under baseline conditions and the second during an insulin infusion. Each scan will include data collected during rest, and a taste task. The taste task involves receiving milkshake or a tasteless solution. After the first scan, an isoglycemic-hyperinsulinemic clamp will be implemented. An IV will be placed in the antecubital vein of of arm for infusion of insulin and dextrose. HumuLIN®-R regular insulin will be infused at 40 mU/m2/min. A second IV will be inserted in the back of the hand on the opposite arm to allow for frequent sampling of blood glucose levels. Dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline value. The study team will monitor blood glucose levels and adjust dextrose infusions as necessary. Thirty minutes after starting the insulin infusion, participants will be moved back into the bore of the MRI scanner for the repeat scans.
Intervention: Insulin
Hyperinsulinemic Clamp
Participants will complete two MRI scans approximately one hour apart - one under baseline conditions and the second during an insulin infusion. Each scan will include data collected during rest, and a taste task. The taste task involves receiving milkshake or a tasteless solution. After the first scan, an isoglycemic-hyperinsulinemic clamp will be implemented. An IV will be placed in the antecubital vein of of arm for infusion of insulin and dextrose. HumuLIN®-R regular insulin will be infused at 40 mU/m2/min. A second IV will be inserted in the back of the hand on the opposite arm to allow for frequent sampling of blood glucose levels. Dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline value. The study team will monitor blood glucose levels and adjust dextrose infusions as necessary. Thirty minutes after starting the insulin infusion, participants will be moved back into the bore of the MRI scanner for the repeat scans.
Intervention: Taste Task
Hyperinsulinemic Clamp
Participants will complete two MRI scans approximately one hour apart - one under baseline conditions and the second during an insulin infusion. Each scan will include data collected during rest, and a taste task. The taste task involves receiving milkshake or a tasteless solution. After the first scan, an isoglycemic-hyperinsulinemic clamp will be implemented. An IV will be placed in the antecubital vein of of arm for infusion of insulin and dextrose. HumuLIN®-R regular insulin will be infused at 40 mU/m2/min. A second IV will be inserted in the back of the hand on the opposite arm to allow for frequent sampling of blood glucose levels. Dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline value. The study team will monitor blood glucose levels and adjust dextrose infusions as necessary. Thirty minutes after starting the insulin infusion, participants will be moved back into the bore of the MRI scanner for the repeat scans.
Intervention: Magnetic Resonance Imaging
Hyperinsulinemic Clamp
Participants will complete two MRI scans approximately one hour apart - one under baseline conditions and the second during an insulin infusion. Each scan will include data collected during rest, and a taste task. The taste task involves receiving milkshake or a tasteless solution. After the first scan, an isoglycemic-hyperinsulinemic clamp will be implemented. An IV will be placed in the antecubital vein of of arm for infusion of insulin and dextrose. HumuLIN®-R regular insulin will be infused at 40 mU/m2/min. A second IV will be inserted in the back of the hand on the opposite arm to allow for frequent sampling of blood glucose levels. Dextrose infusion will be used to keep the blood sugar level within 5mg/dl of the baseline value. The study team will monitor blood glucose levels and adjust dextrose infusions as necessary. Thirty minutes after starting the insulin infusion, participants will be moved back into the bore of the MRI scanner for the repeat scans.
Intervention: Dextrose
Outcomes
Primary Outcomes
fMRI BOLD Response in Brain
Time Frame: During Taste Task in fMRI Scanner. Task Duration is approximately 14 minutes.
The investigators will monitor the blood oxygen level dependent response using fMRI and compare activation during "taste" trials vs. "no taste" trials.