[Incretin and incretin-based therapies].

GIP and GLP-1 are major incretins and secreted from K-cell and L-cell in response to meal ingestion, respectively. GIP and GLP-1 potentiate glucose-induced insulin secretion by binding GIP receptor and GLP-1 receptor, respectively, on pancreatic beta-cell and increasing intracellular cAMP concentration (incretin effect). GIP receptor and GLP-1 receptor are expressed in some different organs. GIP receptor is expressed in intestine, adipose tissue, brain, adrenal gland, and bone, while GLP-1 receptor is expressed in intestine, CNS, lung, kidney and heart. GIP and GLP-1 have not only pancreatic effect, such as potentiation of insulin secretion, but also many extrapancreatic effects. Incretin effect is known to be decreased in type 2 diabetes patients compared to that in healthy subjects. GLP-1 was target peptide as anti-diabetic drug, because insulin secretion in response to GLP-1 infusion was intact in type 2 diabetic patients. GLP-1 mimetics and DPP-4 inhibitor were produced as incretin-based therapy. Type 2 diabetic patients already use them in USA and Europe and get improved glycemic control. Both drugs are reported to improve in Japanese type 2 diabetic patients more glycemic controls compared to those in Caucasian type 2 diabetic patients. Thus, incretin-based therapies may have benefits for Asian patients who have less insulin secretory ability than Caucasian.