title: Incretins: their physiology and application in the treatment of diabetes mellitus.
abstract: Therapies targeting the action of incretin hormones have been under close scrutiny in recent years. The incretin effect has been defined as postprandial enhancement of insulin secretion by gut-derived factors. Likewise, incretin mimetics and incretin effect amplifiers are the two different incretin-based treatment strategies developed for the treatment of diabetes. Although, incretin mimetics produce effects very similar to those of natural incretin hormones, incretin effect amplifiers act by inhibiting dipeptidyl peptidase-4 (DPP-4) enzyme to increase plasma concentration of incretins and their biologic effects. Because glucagon-like peptide-1 (GLP-1) is an incretin hormone with various anti-diabetic actions including stimulation of glucose-induced insulin secretion, inhibition of glucagon secretion, hepatic glucose production and gastric emptying, it has been evaluated as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 also manifests trophic effects on pancreas such as pancreatic beta cell growth and differentiation. Because DPP-4 is the enzyme responsible for the inactivation of GLP-1, DPP-4 inhibition represents another potential strategy to increase plasma concentration of GLP-1 to enhance the incretin effect. Thus, anti-diabetic properties of these two classes of drugs have stimulated substantial clinical interest in the potential of incretin-based therapeutic agents as a means to control glucose homeostasis in T2DM patients. Despite this fact, clinical use of GLP-1 mimetics and DPP-4 inhibitors have raised substantial concerns owing to possible side effects of the treatments involving increased risk for pancreatitis, and C-cell adenoma/carcinoma. Thus, controversial issues in incretin-based therapies under development are reviewed and discussed in this manuscript.
authors.forename: Hale M
authors.initials: HM
authors.lastname: Tasyurek
authors.forename: Hasan Ali
authors.initials: HA
authors.lastname: Altunbas
authors.forename: Mustafa Kemal
authors.initials: MK
authors.lastname: Balci
authors.forename: Salih
authors.initials: S
authors.lastname: Sanlioglu
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000077270:Exenatide; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000502:physiology / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000009:adverse effects / Q000502:physiology* / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000069036:Insulin Glargine; D000078790:Insulin Secretion; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists / Q000187:drug effects; D014688:Venoms / Q000627:therapeutic use
chemical_list: D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitors; GLP-1; GLP-1 analogues; diabetes; incretins