Glycogenolytic activity of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in vivo and in vitro

Sekiguchi, Yoshio; Kasai, Kikuo; Hasegawa, Kaoru; Suzuki, Yoshinobu; Shimoda, Shin-Ichi

doi:10.1016/0024-3205(94)00661-x

Cited by 36 publications

(41 citation statements)

References 14 publications

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“…(i) The dose of PACAP injected i.c.v. in our study was much lower than the minimum effective doses of PACAP administered intravenously (Sekiguchi et al, 1994;Ozawa et al, 1999). In addition, it should be noticed that the half-life of PACAP38 in the systemic circulation is very short (E3.5 min; Birk et al, 2007;Bourgault et al, 2008) so that any PACAP diffusing from the brain to the periphery would be rapidly degraded.…”

Section: Discussioncontrasting

confidence: 54%

“…injection of PACAP produces hyperglycemia without affecting plasma corticosterone level. It is now firmly established that peripheral administration of PACAP also provokes a significant increase in plasma glucose level (Sekiguchi et al, 1994;Ozawa et al, 1999). Although PACAP can be transported out of the brain (Banks et al, 1993), two observations indicate that the effect of centrally-administered PACAP on glucose homeostasis cannot be accounted for by a peripheral action of the peptide.…”

Section: Discussionmentioning

confidence: 99%

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Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

Mounien

Rego

Bizet

et al. 2008

Neuropsychopharmacol

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide, a-melanocytestimulating hormone (a-MSH), exert anorexigenic activities. While a-MSH is known to inhibit food intake and stimulate catabolism via activation of the central melanocortin-receptor MC4-R, little is known regarding the mechanism by which PACAP inhibits food consumption. We have recently found that, in the arcuate nucleus of the hypothalamus, a high proportion of POMC neurons express PACAP receptors. This observation led us to investigate whether PACAP may inhibit food intake through a POMC-dependent mechanism. In mice deprived of food for 18 h, intracerebroventricular administration of PACAP significantly reduced food intake after 30 min, and this effect was reversed by the PACAP antagonist PACAP6-38. In contrast, vasoactive intestinal polypeptide did not affect feeding behavior. Pretreatment with the MC3-R/MC4-R antagonist SHU9119 significantly reduced the effect of PACAP on food consumption. Central administration of PACAP induced c-Fos mRNA expression and increased the proportion of POMC neuronexpressing c-Fos mRNA in the arcuate nucleus. Furthermore, PACAP provoked an increase in POMC and MC4-R mRNA expression in the hypothalamus, while MC3-R mRNA level was not affected. POMC mRNA level in the arcuate nucleus of PACAP-specific receptor (PAC1-R) knock-out mice was reduced as compared with wild-type animals. Finally, i.c.v. injection of PACAP provoked a significant increase in plasma glucose level. Altogether, these results indicate that PACAP, acting through PAC1-R, may inhibit food intake via a melanocortin-dependent pathway. These data also suggest a central action of PACAP in the control of glucose metabolism.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

Mounien

Rego

Bizet

et al. 2008

Neuropsychopharmacol

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“…When rats were given an intravenous injection of 1 nmol/kg of the VPAC1-selective agonist [K15, R16, L27]VIP(1-7)/ GRF (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), it increased plasma insulin levels by twofold, but, consistent with the role of VPAC1 in enhancing hepatic glucose production, it also increased blood glucose levels by 14% 30 min after an IPGTT (data not shown). The VPAC1-selective agonist displayed dosedependent effects on intestinal water retention that were identical to those of VIP, whereas the effect of the VPAC2-selective agonist was much less.…”

Section: Vpac2 Agonist For Type 2 Diabetesmentioning

confidence: 71%

A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal

et al. 2002

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Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) activate two shared receptors, VPAC1 and VPAC2. Activation of VPAC1 has been implicated in elevating glucose output, whereas activation of VPAC2 may be involved in insulin secretion. A hypothesis that a VPAC2-selective agonist would enhance glucose disposal by stimulating insulin secretion without causing increased hepatic glucose production was tested using a novel selective agonist of VPAC2. This agonist, BAY 55-9837, was generated through site-directed mutagenesis based on sequence alignments of PACAP, VIP, and related analogs. The peptide bound to VPAC2 with a dissociation constant (K d ) of 0.65 nmol/l and displayed >100-fold selectivity over VPAC1. BAY 55-9837 stimulated glucose-dependent insulin secretion in isolated rat and human pancreatic islets, increased insulin synthesis in purified rat islets, and caused a dose-dependent increase in plasma insulin levels in fasted rats, with a half-maximal stimulatory concentration of 3 pmol/kg. Continuous intravenous or subcutaneous infusion of the peptide reduced the glucose area under the curve following an intraperitoneal glucose tolerance test. The peptide had effects on intestinal water retention and mean arterial blood pressure in rats, but only at much higher doses. BAY 55-9837 may be a useful therapy for the treatment of type 2 diabetes.

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“…However, this is also an unlikely explanation because PACAP has been shown to stimulate glucose uptake in adipocyte cell line 3T3L1 (87). Two remaining possibilities are that PACAP stimulates the glucose output from the liver, which has been demonstrated in vitro (56,57), and that PACAP indirectly stimulates hepatic glucose output through stimulation of epinephrine release from the adrenals. This latter explanation is supported by the finding that PACAP increases plasma epinephrine levels in mice (79); epinephrine is known to antagonize insulin action (88).…”

Section: Islet Physiology Of Pacapmentioning

confidence: 99%

“…Liver. PACAP exerts direct effects on the liver, as shown by stimulation of glucose output from the perfused rat liver and from cultured rat hepatocytes by an effect mediated by a cAMP-dependent stimulation of glycogenolysis and is also accompanied by an increase in intracellular Ca 2ϩ (56,57). Vasculature.…”

Section: Pacapmentioning

confidence: 99%

The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

2001

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The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is ubiquitously distributed in both the central and peripheral nervous systems and exerts a variety of effects. PACAP is a neuropeptide in pancreatic islets, where it has been suggested as a parasympathetic and sensory neurotransmitter. PACAP stimulates insulin secretion in a glucose-dependent manner, by an effect executed mainly through augmenting the formation of cAMP and stimulating the uptake of calcium. Accumulating evidence in animal studies points to a physiological importance of PACAP in the regulation of the insulin response to feeding. This review summarizes the current knowledge of islet actions and mechanisms and the function of PACAP. Diabetes 50: 1959

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Glycogenolytic activity of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in vivo and in vitro

Cited by 36 publications

References 14 publications

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal

The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

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