The glucagon-like peptides: a double-edged therapeutic sword?

Glucagon-like peptide-1(7-36)-amide (GLP-1) is an endogenous peptide that is secreted from the gut in response to the presence of food. Recent studies have established that GLP-1 and its longer-acting analog exendin-4 have multiple synergistic effects on glucose-dependent, insulin secretion pathways of the pancreatic beta-cell and on plasticity in neuronal cells. Recent interest has focused on the development of these peptides as a novel therapeutic strategy for non-insulin-dependent (type 2) diabetes mellitus and associated neuropathy. This is with a view to developing lead compounds, based on neurotrophic action, for central and peripheral degenerative disorders such as stroke and Alzheimer's disease in addition to the peripheral neuropathy associated with type 2 diabetes mellitus. Here, we address recent advances in the biological action of GLP-1 and its related analogs.