Neural Pathways and Neuropeptides Mediate the Therapeutic Actions of DPP IV Inhibitors in Type-2 Diabetes

Author(s): Adnan Erol

Journal Name: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued)

Volume 1 , Issue 2 , 2007


In response to nutrient intake, glucagon-like peptide-1 (GLP-1), which is considered as an incretin, is secreted from endocrine cells in gastrointestinal mucosa. With respect to the incretin effect function of GLP-1, which is reduced significantly in type 2 diabetes mellitus, how does such a minor amount of secreted peptide augment insulin secretion by hormonally transduced signals from the gut even at stabilized endogenous physiolgical concentrations of GLP-1 by DPP-IV inhibitors? It is necessary to get a satisfactory mechanistic explanation to positive preliminary clinical studies done with dipeptidyl peptidase-IV (DPP-IV) inhibitors in type-2 diabetics. The regulation of neurally mediated insulin secretion is still neglected concept. GLP-1 and particularly glucose-dependent insulinotropic polypeptide (GIP) are exerted not only through a direct action on the beta cells but may be dependent on indirectly mediated sensory afferent nerves. Pluripotent glycoprotein enzyme DPP-IV is a ubiquitously distributed, and inactivates a number of biologically active peptides such as GIP, pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin-releasing peptide (GRP), and glucagon itself, which all have efficient insulinotropic potential. In addition, it has been shown that DPP-IV inhibitors work in the central nervous system regulating the function of neuropeptides. A novel proposal for the mechanism of action of DPP-IV inhibitors and related patents will be discussed in the paper.

Keywords: DPP-IV inhibitors, type-2 diabetes, glucagons-like peptide-1 (GLP-1), gastrin-releasing peptide (GRP), pituitary adenylate cyclase-activating polypeptide (PACAP)

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Article Details

Year: 2007
Page: [132 - 135]
Pages: 4
DOI: 10.2174/187221407780831966
Price: $58

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