Pleiotropic effects of incretins.

ABSTRACT

Drugs that augment the incretin system [glucagon like peptide (GLP) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors] represent a novel class of anti-hyperglycemic agents that have shown to improve the health and survival of beta-cells (improvement in postprandial hyperglycemia) and suppress glucagon (improvement in fasting hyperglycemia). The incretins represent a large family of molecules referred to as the "glucagon superfamily of peptide hormones" of which more than 90% of the physiological effects of incretins are accomplished by GLP-1(7-37) and GLP1(7-36) amide and gastric insulinotropic peptide (GIP). GLP-1 mediates its effects via the GLP-1 receptor, which has a wide tissue distribution [pancreas, lung, heart, vascular smooth muscle cells, endothelial cells, macrophages and monocytes, kidney, gastrointestinal tract (stomach and intestine), central nervous system (neoortex, cerebellum, hypothalamus, hippocampus, brainstem nucleus tractus solitarius) and peripheral nervous system]. This would imply that the incretin system has effects outside the pancreas. Over time data has accumulated to suggest that therapies that augment the incretin system has beneficial pleiotrophic effects. The incretins have shown to possess a cardiac-friendly profile, preserve neuronal cells and safeguard from neuronal degeneration, improve hepatic inflammation and hepatosteatosis, improve insulin resistance, promote weight loss and induce satiety. There is growing evidence that they may also be renoprotective promoting wound healing and bone health.