Obesity101.com THE LATEST IN OBESITY RESEARCH AND WEIGHTLOSS DRUG DEVELOPMENT Join our list More information Glucagon-like peptide. Glucagon-like peptide 1 (GLP-1) is a gut peptide that has been under investigation for use as both a diabetes and obesity medication. Unlike current medications that affect catecholamine and serotonin pathways, GLP-1 inhibits gastric emptying. Delayed gastric emptying limits food intake, stimulates insulin, and inhibits glucagon secretion after a meal. In diabetics this action reduces postprandial hypoglycemia, and may result in weight loss. THE ILEAL BRAKE MECHANISM E. the ileal brake mechanism inhibits gastric emptying, inhibits food intake, stimulates insulin and inhibits glucagon secretion afer a meal GLP-1 may affect the "ileal brake mechanism", an important regulator of gastrointestinal function. Unabsorbed nutrients in the ileum, especially fat, inhibit gastric emptying, decrease intestinal motility, transit and pancreatic secretions. Researchers speculate that vagal activity may contribute to the inhibitory effect of GLP-1 on gastric emptying. Many studies have shown that obese patients have accelerated gastric emptying and weaker GLP-1 and cholecystokinin (CCK) response as compared to lean controls. Both weight loss and gastric surgery have been shown to decrease the rate. In a recent study, a group of 20 men ate less and felt fuller when infused with GLP-1 than when given placebo. Subjects. 20 normal weight non-smoking men ages 20-31 years old with a body mass index (BMI) of 20.3 to 25.7 and body fat percentage of 9.7 to 19.5 percent. The men had no family history of obesity or diabetes and were not "elite athletes". One subject was excluded from the data analysis because of a severe headache on the second day. Method. The subjects were tested on two occasions in a placebo-controlled, randomized, blinded, crossover study. The two test days were separated by at least three weeks, but not more than seven. Subjects restrained from strenuous physical activity and ate a weight-maintaining, standardized diet for 2 days before the study. On the date of the experiment the men were told to take the least strenuous means of transportation to the site. They rested for 45 minutes after arriving at the facility, and then a fasting blood sample was taken. Two different test meals were used, a fixed-size breakfast and an "ad libitum" lunch. Results. The men receiving the GLP-1 infusion reported enhanced satiety after breakfast and ate 12 percent less at lunch. GLP-1 and obesity. There have been few studies on the effect of GLP-1 in obese people. But those studies show that it is likely to promote weight loss. A 1997 study showed comparable glucose lowering effects in both lean and obese subjects with type-2 diabetes, indicating that GLP-1 receptors function normally in the obese. 1 These findings suggest that GLP-1 will normalize the accelerated gastric emptying in obese people, and reverse morbid obesity. Two hurdles need to be overcome before GLP-1 can be produced for use in patients 1) an oral formulation of GLP-1 needs to be developed, and 2) testing on long term appetite suppression needs to be conducted. As a peptide, GLP-1 cannot be taken orally since it is metabolized rapidly. The intact peptide only stays in circulation for 1.5 minutes. The experiment above used continuous infusion. Because of the method of testing, long term human trials on GLP-1 and appetite have not been conducted. A 1998 rat study showed that continuous GLP-1 infusion to the third ventricle over a six day period only provided appetite control on day 1. There was partial reduction on day 2, and no effect on appetite thereafter. Further, none of the rats experienced any weight loss. Researchers in the rat study concluded that GLP-1 was not a long-term regulator of caloric intake and body weight in the central nervous system (CNS). 2 Whether this proves to be true in humans, remains to be seen. Dr. Joel Habener of Harvard University says that an oral formulation of GLP-1 could be made available within two to three years. At that time, long term study on appetite suppression in humans can be conducted. Flint A, et al. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. (medline) J Clin Invest. 1998 Feb 1; 101(3): 515-520. Toft-Nielsen MB, et al. Iv glucagon-like peptide-1 (GLP-1) lowers blood glucose levels in NIDDM patients regardless of fasting glucose, BMI, and insulin capacity. Diabetes 46(Suppl. 1):A189. Donahey JCK, et al. Intraventricular GLP-1 reduces short- but not long-term food intake or body weight in lean and obese rats. Brain Res. 1998 Jan 1; 779(1-2): 75-83. (medline) Home|Subscribe|Archives|Drug info|Contact|Media & Links|Site index|FAQs|Doctors/meetings|Admin Obesity-news is a publication of Hirsch Communications. An on-line subscription is $104.00 per year, payable in advance by check, money order, American Express, Discover, VISA or Mastercard. Subscribing is simple using our secure on-line subscription form. Obesity-news also accepts fax orders at 703/960-7462 and mail orders at PO Box 19316, Alexandria, VA 22320-0316. Copyright 1997-2008, all rights reserved. IMPORTANT: All information in this publication is believed to be accurate and true. Publisher is not liable for omissions or inaccuracies. Information in this newsletter is for educational purposes only and should not be construed as medical advice, or be used in lieu of consultation with a health care provider.