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New therapeutic molecules targeting glucagon-like peptides 1 and 2

The latest issue of the Alimentary Pharmacology & Therapeutics reviews the discovery of new therapeutic molecules targeting GLP-1 and GLP-2.

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Recent advancements in understanding the roles and functions of glucagon-like peptide 1 (GLP-1) and 2 (GLP-2) have provided a basis for targeting these peptides in therapeutic strategies.

Professor Tack and colleagues from Belgium summarized the preclinical, and clinical research supporting the discovery of new therapeutic molecules targeting GLP-1 and GLP-2.
 
The research team performed a comprehensive PubMed search, representing literature published during the past 30 years related to GLP-1 and GLP-2.

GLP-2R is expressed almost exclusively in the stomach and bowel
Alimentary Pharmacology & Therapeutics

Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP-1 and GLP-2 exhibit distinctive biological functions that are governed by the expression of their respective receptors, GLP-1R and GLP-2R.

Through widespread expression in the pancreas, intestine, and nervous tissue, GLP-1Rs facilitates an incretin effect along with effects on appetite and satiety.

GLP-1 analogues resistant to degradation by dipeptidyl peptidase-IV and inhibitors of dipeptidyl peptidase-IV have been developed to aid treatment of diabetes, and obesity.

The team report that the GLP-2R is expressed almost exclusively in the stomach and bowel.

The most apparent role for GLP-2 is its promotion of growth and function of intestinal mucosa, which has been targeted for therapies that promote repair and adaptive growth.

The team noted that these are used as treatments for intestinal failure and related conditions.
 
Professor Tack's team concludes, "Our growing understanding of the biology and function of GLP-1, GLP-2 and corresponding receptors has fostered further discovery of fundamental biological function as well as new categories of potent therapeutic medicines."

Aliment Pharmacol Ther 2012: 37(1): 18–36
06 December 2012

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