[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.
Harada
Norio
N
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University.
Inagaki
Nobuya
N
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D054795:Incretins / Q000502:physiology* / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists
D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D018027:Receptors, Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4