Glucagon-like peptide 1(GLP-1) in biology and pathology.
Post-translational proteolytic processing of the preproglucagon gene in the gut results in the formation of glucagon-like peptide 1 (GLP-1). Owing to its glucose-dependent insulinotropic effect, this hormone was postulated to primarily act as an incretin, i.e. to augment insulin secretion after oral glucose or meal ingestion. In addition, GLP-1 decelerates gastric emptying and suppresses glucagon secretion. Under physiological conditions, GLP-1 acts as a part of the 'ileal brake', meaning that is slows the transition of nutrients into the distal gut. Animal studies suggest a role for GLP-1 in the development and growth of the endocrine pancreas. In light of its multiple actions throughout the body, different therapeutic applications of GLP-1 are possible. Promising results have been obtained with GLP-1 in the treatment of type 2 diabetes, but its potential to reduce appetite and food intake may also allow its use for the treatment of obesity. While rapid in vivo degradation of GLP-1 has yet prevented its broad clinical use, different pharmacological approaches aiming to extend the in vivo half-life of GLP-1 or to inhibit its inactivation are currently being evaluated. Therefore, antidiabetic treatment based on GLP-1 may become available within the next years. This review will summarize the biological effects of GLP-1, characterize its role in human biology and pathology, and discuss potential clinical applications as well as current clinical studies.
Meier
Juris J
JJ
Larry L. Hillblom Islet Research Center, UCLA School of Medicine, Los Angeles, USA.
Nauck
Michael A
MA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry / Q000502:physiology; D005934:Glucagon / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D006801:Humans; D010446:Peptide Fragments / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use; D011498:Protein Precursors / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use
D001786:Blood Glucose; D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon