Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): The role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress.

Glucagon-like peptide-1 (GLP-1) is produced both in the human and rat intestineand brain. The release of GLP-1 into the blood is mediated by factors of neural and hormonal origin andis stimulated by the presence of nutrients in the digestive tract, while the enzyme dipeptidyl peptidaseIV and the kidneys are responsible for, respectively, the rapid degradation and excretion of the hormone.Peripherally secreted GLP-1 enhances insulin synthesis and release and maintains the normal anatomicalstatus of pancreatic islets. Diminished GLP-1 response to ingested food, associated with attenuated insulinrelease and glucose intolerance, was found in non-insulin-dependent diabetes mellitus. GLP-1 replacementin diabetic subjects normalized these parameters, thus indicating a role for this peptide in the pathogenesisof type 2 diabetes. GLP-1 might also be involved in the pathophysiology of obesity and stress to someextent. Both peripheral and central GLP-1 are probably involved in the control of feeding centers asan anorexic agent. GLP-1 affects the activity of the hypothalamo-pituitary-adrenal axis both under basaland stress conditions, including taste aversion learning. Hence, GLP-1-dependent pathophysiological mechanismsmay participate in the pathogenesis of the most common metabolic and behavioral disorders.

Keywords: Obesity - metabolism, Peptide Fragments - secretion, Protein Precursors - secretion, Animals, Diabetes Mellitus - metabolism, Glucagon - secretion, Glucagon-Like Peptide 1, Obesity - metabolism, Pancreas - metabolism, Peptide Fragments - secretion, Protein Precursors - secretion, Stress, Physiological - metabolism