The incretin abc's in helath and disease-novel approaches to obesity and diabetes treatment

Abstract

Abstract Incretins are gastrointestinal-derived hormones released in response to a meal that play a key role in the regulation of postprandial secretion of insulin (incretin effect) and glucagon by the pancreas. Both incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have several other actions. GLP-1 regulates body weight by inhibiting appetite and delaying gastric emptying, actions that are dependent on central nervous system GLP-1 receptor activation. Several other hormones and gut peptides, including leptin and ghrelin, interact with GLP-1 to modulate appetite. GLP-1 is labile, being rapidly degraded by dipeptidyl peptidase-4 (DPP-4), a multifunction molecule whose role in obesity dynamics extends beyond incretin metabolism. DPP-4 is involved in adipose tissue inflammation, which is a pivotal event in insulin resistance and a key pathophysiological mechanism in the genesis of obesity-related complications. Furthermore, the incretin system appears to provide the basis for understanding the high weight loss efficacy of bariatric surgery, a current employed obesity treatment that also benefits diabetes. The present review brings together new insights into obesity pathogenesis, integrating GLP-1 and DPP-4 in the complex interplay between obesity epidemics and inflammation, namely in diabetic patients. This will in turn provide the basis for new perspectives regarding GLP-1 receptor agonists and DPP-4 inhibitors therapeutic potential.