Incretins and Their Endocrine and Metabolic Functions

Incretins are hormones secreted into the blood stream from the gut mucosa in response to nutrient intake. They have been characterized based on their capacity to lower blood glucose levels. The more potent reduction of blood glucose coupled to a more intensive stimulation of insulin secretion, in response to oral glucose uptake, as compared to intravenous glucose infusion has further been termed the "incretin effect." As a prototype incretin hormone, the biology of glucagon-like peptide 1 (GLP-1) has been intensively studied. GLP-1 actions are mediated through cyclic adenosine monophosphate-coupled membrane receptors. Classical physiological effects involve stimulation of insulin secretion from pancreatic beta cells and reduction of glucagon secretion from pancreatic alpha cells, inhibition of gastric motility, and increase of satiety with reduced food uptake. The understanding of these metabolic functions has led to the notion that incretin hormones, and specifically GLP-1, would represent ideal antidiabetic treatment options. As native GLP-1 is degraded by dipeptidyl peptidase type 4 (DPP-4) within minutes, other pharmacological approaches to exploit GLP-1 actions for the treatment of type 2 diabetes have been developed. These include DPP-4 inhibitors as oral medications and GLP-1 receptor agonists (incretin mimetics) as peptide compounds to be injected.