Long-term administration of PACAP receptor antagonist, PACAP(6-27), impairs glucose tolerance and insulin sensitivity in obese diabetic ob/ob mice.

Abstract

Pituitary adenylate cyclase-activating peptide (PACAP) is a ubiquitous peptide of the glucagon superfamily that is involved in glucose homeostasis and regulation of insulin secretion. This study employed the PACAP receptor antagonist, PACAP(6-27) to evaluate the role of endogenous PACAP in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob mice. Acute in vivo antagonistic potency of PACAP(6-27) was confirmed in ob/ob mice by blockade of the insulin-releasing action but not hyperglycaemia. In longer-term studies, ob/ob mice were given once daily injections of PACAP(6-27) or vehicle for 14 days. Feeding activity, body weight, basal plasma glucose and plasma insulin concentrations were not significantly affected by chronic PACAP(6-27) treatment. However, PACAP(6-27) treatment impaired glucose tolerance, insulin sensitivity and the glycaemic response to feeding. Plasma glucagon and lipids were unchanged. These observations indicate a role of endogenous PACAP for normal glucose homeostasis, but indicate a minor involvement in the regulation of insulin secretion in ob/ob mice.

• Authors: Brian D Green, Nigel Irwin, Roslyn S Cassidy, Victor A Gault, Peter R Flatt
• Journal: Peptides (Peptides) Vol. 27 Issue 9 Pg. 2343-9 (Sep 2006) ISSN: 0196-9781 [Print] United States
• PMID: 16730098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Lipids
• Peptide Fragments
• Pituitary Adenylate Cyclase-Activating Polypeptide
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
• pituitary adenylate-cyclase-activating peptide (6-27)
• Glucagon

Topics

• Animals
• Body Weight (drug effects)
• Diabetes Mellitus (blood, etiology, metabolism)
• Eating (drug effects)
• Feeding Behavior (drug effects)
• Glucagon (blood, metabolism)
• Glucose Intolerance (blood)
• Insulin (blood, pharmacology)
• Lipids (blood)
• Mice
• Mice, Obese
• Obesity (complications)
• Peptide Fragments (administration & dosage, pharmacology)
• Pituitary Adenylate Cyclase-Activating Polypeptide (administration & dosage, pharmacology)
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide (antagonists & inhibitors, metabolism)
• Time Factors