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Exendin-4 potently decreases ghrelin levels in fasting rats.

Perez-Tilve D, Gonzalez-Matias L, Alvarez-Crespo M, Leiras R, Tovar S, Dieguez C, Mallo F.

Diabetes. 2007 Jan;56(1):143-51

Summary by Jamie H. Bassel, D.C., P.C. 

Ghrelin is a hormone produced the stomach that stimulates appetite. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone leptin, produced by fatty tissue, which causes a sense of fullness when present at higher levels. Ghrelin also stimulates the secretion of growth hormone from the anterior pituitary gland. Increased amounts of Ghrelin circulating in the bloodstream increases food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is a molecule that selectively binds to a specific glucagon-like peptide (GLP-1) receptor (GLP1-r). (GLP-1r) when stimulated has the ability to reduce the desire to eat and stimulates fat-reduction. The researchers in this study were able to demonstrate that Ex-4 reduced Ghrelin levels by 74% in fasting rats. This phenomenon was observed when Ex-4 was administered directly into the brain and intravenously. The reduction of circulating ghrelin was not replicated to the same extent by other substances that could bind to the GLP-1r and the receptor could not be blocked by anything other than Ex-4. Another interesting finding revealed that Ex-4 binding to the GLP-1 receptor occurred independently of the insulin and leptin levels. The effect that Ex-4 has on Ghrelin levels may account for the decrease in appetites in fasting rats, which further explains the stronger reduction in appetite when compared to GLP-1. The use of Ex-4 in reducing the circulating Ghrelin levels may have a therapeutic benefit in controlling appetite in PWS as well as type II Diabetes.

Abstract - click here

edited: 02/09/2012

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