The Role of GLP-1 in Satiety Perception in Humans
Scientists have discovered a number of hormones that control our feelings of hunger and fullness. One particular hormone, called GLP-1, has been associated with feelings of hunger and fullness. The overall purpose of this study is to look more closely at how GLP-1 changes these feelings and to observe how these hormones affect the brain's function. To do this, volunteers will be asked to come to the clinic for a screening visit, and 2 study visits. This is an outpatient study with a screening visit which will last about an hour and the two subsequent study visits for about 3 hours each. During the study, patients will receive a drug that blocks the effect of a hormone made in the gut. We will take a series of blood samples to measure hormones and use functional magnetic resonance imaging (MRI) to take pictures of the brain. Understanding the action of these hormones in the brain may eventually lead to new ways to help people avoid obesity or lose weight.
Many times each day, we see food or representations of food and evaluate whether or not the food looks good to us. If it does, we then balance external factors, such as the social situation or time of day, against internal signals about our hunger state in order to decide what and when to eat. However, recent functional magnetic resonance imaging (fMRI) studies suggest that internal signals, such as hormones regulating appetite and satiety, govern our food intake in part by acting on neural circuits to affect whether a given food appears appetizing at that moment. In addition, photographs of food perceived to be "fattening" activate brain regions involved in appetite and reward processing, including the hypothalamus, nucleus accumbens, and orbital frontal cortex. This activity is potently reduced by food intake, suggesting that it reflects underlying brain mechanisms involved in satiety. We now propose to study the mechanism of these changes in brain activity by asking if they are directly related to the action of glucagon-like peptide-1 (GLP-1), a satiety signal. GLP-1 is released by cells in the gut in response to nutrients, suppressing food intake, and its actions can be blocked by a GLP-1 receptor antagonist, exendin-[9-39]. In 2 randomized, controlled, crossover studies, we will assess whether exendin-[9-39] infusions reverse GLP-1-mediated effects on food intake and on brain response to visual food cues. Our scientific aims are to 1) observe the effect of exendin (9-39) on blocking GLP-1-mediated satiety in humans and assess its effect on food intake in humans for the first time (to our knowledge) and 2) to test whether endogenous GLP-1 signaling is required for the effect of a meal to reduce brain response to visual food cues in humans. We hypothesize that exendin-[9-39] will diminish the effect of a meal in suppressing subsequent food intake and in reducing activation to visual food cues in reward pathways. Determining the extent to which the experience of satiety arises from a decrease in the reward value of food is fundamentally important to understanding human feeding behavior. In addition, this promising line of research is directly relevant to some of the most pressing public health issues of our time: obesity and overnutrition. We hope that investigating mechanisms affecting our perception of satiety at the most basic level will eventually result in novel behavioral or pharmacologic strategies for obesity prevention and treatment.
Allocation: Randomized, Control: Placebo Control, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science
Exendin-(9-39) Acetate, Saline 0.9%
University of Washington
Not yet recruiting
University of Washington
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT01152333
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Physiologic mechanisms which regulate or control the appetite and food intake.
Natural recurring desire for food. Alterations may induced by APPETITE DEPRESSANTS or APPETITE STIMULANTS.
Agents that are used to decrease appetite.
Agents that are used to stimulate appetite. These drugs are frequently used to treat anorexia associated with cancer and AIDS.
A genus of HALOBACTERIACEAE distinguished from other genera in the family by the presence of specific derivatives of TGD-2 polar lipids. Haloarcula are found in neutral saline environments such as salt lakes, marine salterns, and saline soils.
The objective of this project is to understand defects in insulin secretion that contribute to abnormal glucose metabolism in patients with diabetes.
To evaluate the short-term effects of structured lipids on appetite regulation.
The purpose of this study is to determine the dose of the GLP-1 receptor antagonist exendin(9-39) which blocks the insulinotropic action of synthetic GLP-1 by at least 95%.
The purpose of this study is to determine if Exendin-(9-39), an antagonist of the glucagon-like peptide-1 (GLP-1) receptor with effects on the pancreatic beta cell, increases fasting bloo...
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PURPOSE: Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is tran...