Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus

• Published in: The international journal of biochemistry & cell biology 2006-01, Vol.38 (5), p.845-859
• Main Authors: León, Diva D. De, Crutchlow, Michael F., Ham, Jee-Young Nina, Stoffers, Doris A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Blood Glucose - metabolism; Diabetes; Diabetes Mellitus - drug therapy; Diabetes Mellitus - etiology; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - etiology; Dipeptidyl Peptidase 4 - metabolism; GLP-1; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - physiology; Glucagon-Like Peptide 1 - therapeutic use; Glucagon-Like Peptide-1 Receptor; Glucose; Homeostasis; Humans; Insulin; Liraglutide; Maleimides - therapeutic use; Molecular Sequence Data; Nitriles - therapeutic use; Peptides - therapeutic use; Protease Inhibitors - therapeutic use; Pyrrolidines - therapeutic use; Receptors, Glucagon - agonists; Venoms - therapeutic use; β Cells
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2005.07.011

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L cells in response to ingested nutrients. The first recognized and most important action of GLP-1 is the potentiation of glucose-stimulated insulin secretion in β-cells, mediated by activation of its seven transmembrane domain G-protein-coupled receptor. In addition to its insulinotropic actions, GLP-1 exerts islet-trophic effects by stimulating replication and differentiation and by decreasing apoptosis of β-cells. The GLP-1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism, including pancreatic α-cells, hypothalamus and brainstem, and proximal intestinal tract. GLP-1 also appears to exert important actions in liver, muscle and fat. Thus, GLP-1 suppresses glucagon secretion, promotes satiety, delays gastric emptying and stimulates peripheral glucose uptake. The impaired GLP-1 secretion observed in type 2 diabetes suggests that GLP-1 plays a role in the pathogenesis of this disorder. Thus, because of its multiple actions, GLP-1 is an attractive therapeutic target for the treatment of type 2 diabetes, and major interest has resulted in the development of a variety of GLP-1 receptor agonists for this purpose. Ongoing clinical trials have shown promising results and the first analogs of GLP-1 are expected to be available in the near future.