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Pituitary adenylate cyclase-activating peptide (PACAP): Assessment of dipeptidyl peptidase IV degradation, insulin-releasing activity and antidiabetic potential

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Green, BD, Irwin, Nigel and Flatt, Peter (2006) Pituitary adenylate cyclase-activating peptide (PACAP): Assessment of dipeptidyl peptidase IV degradation, insulin-releasing activity and antidiabetic potential. PEPTIDES, 27 (6). pp. 1349-1358. [Journal article]

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DOI: 10.1016/j.peptides.2005.11.010

Abstract

Pituitary adenylate cyclase-activating peptide (PACAP) is a member of the glucagon family of peptides. Like other members, most notably glucagon-like peptide-1 (GLP-1), PACAP is rapidly degraded by dipeptidylpeptidase IV (DPP IV). This study investigated how degradation by DPP IV affected the insulinotropic activity of PACAP, and whether PACAP exerted acute antihyperglycemic properties in normal or ob/ob mice. DPP IV degradation of PACAP(127) over 18 h led to the formation of PACAP(3-27), PACAP(5-27) and ultimately PACAP(6-27). In contrast to 1.4-1.8-fold concentration-dependent stimulation of insulin secretion by PACAP(1-27), these peptide fragments lacked insulinotropic activity. While PACAP(1-27) and PACAP(1-38) generated significant insulin responses when given alone or together with glucose in ob/ob and normal mice, they also elevated plasma glucose. These actions were eliminated following degradation of the peptide by incubation with DPP IV. The hyperglycemic effects may be explained at least partly by a potent glucagon-releasing action in ob/ob and normal mice. In conclusion, PACAP is inactivated by DPP IV and despite insulin-releasing effects, its actions on glucagon secretion and glucose homeostasis do not make it a good therapeutic tool for the treatment of type 2 diabetes. (c) 2005 Elsevier Inc. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2978
Deposited By:Professor Peter Flatt
Deposited On:18 Dec 2009 09:23
Last Modified:19 Nov 2012 16:08

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