Pancreatic endocrine responses to the peptides VIP and PACAP in the conscious calf

Abstract

SUMMARYPancreatic endocrine responses to vasoactive intestinal peptide (VIP), pituitary adenylate cyclaseactivating peptide (PACAP) and acetylcholine have been investigated in conscious calves, while continuously monitoring aortic blood pressure and heart rate, in order to assess the effects of these neuropeptides under normal physiological conditions. VIP was found to modulate the release of pancreatic polypeptide (PP) in response to acetylcholine at a dose which had no significant effect on the release of either pancreatic glucagon or insulin. PACAP stimulated the release of insulin and the effect was potentiated during infusions of exogenous glucose. PACAP, when infused together with acetylcholine, also stimulated the release of pancreatic glucagon in the absence of exogenous glucose but not in its presence. Release of PP was stimulated during infusions of PACAP, whether or not exogenous glucose was given, and this effect was found to be additive with that of acetylcholine.

The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

“…In some cases, the flushing was of long duration and remained Ͼ12 h after termination of the infusion, which corroborates with the slow dissociation of PACAP from its receptors (59). Systolic and diastolic blood pressures decreased by ϳ10 mmHg, and pulse rates increased by 15 beats per min, which is in accordance with the results obtained in calves (77). The results show that PACAP slightly increased serum insulin levels in the overnight-fasted healthy volunteers and potentiated the insulin and C-peptide responses to an intravenous glucose challenge (28).…”

“…In addition, glucagon secretion in vivo is stimulated by PACAP, as demonstrated in mice (60,79), dogs (78), and humans (28), whereas in calves, PACAP augments acetylcholine-stimulated glucagon secretion without having any direct effect per se (77). Furthermore, administration of glucose inhibits PACAP-induced glucagon secretion (28,(77)(78)(79), showing that the action is glucose sensitive.…”

“…In vivo. PACAP stimulates insulin secretion in vivo in several species of experimental animals, such as calves (77), dogs (78), and mice (60,79). In both calves and mice, PACAP and VIP stimulate insulin secretion equipotently, and in mice it has also been demonstrated that PACAP27 and PACAP38 are equipotent (79).…”

“…Furthermore, administration of glucose inhibits PACAP-induced glucagon secretion (28,(77)(78)(79), showing that the action is glucose sensitive. Finally, PACAP seems to have vasodilatory action in the pancreas, as demonstrated in vivo in rats (81) and in the perfused rat pancreas (72).…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…In vivo administration of PACAP causes a significant increase in plasma insulin level in mice (Fridolf et al, 1992;Filipsson et al, 1998a;Persson-Sjögren et al, 2006), calf (Edwards et al, 1997), dog (Kawai et al, 1992), and human (Filipsson et al, 1997). In support of a role of PACAP on islet hormone secretion (Yada et al, 1997a), PACAP knock-out mice or animals treated with the antagonist PACAP(6 -38) exhibit reduced insulin secretion after intraperitoneal glucose challenge Green et al, 2006;Tomimoto et al, 2008).…”