Evidence for Contribution by Increased Cytoplasmic Na+ to the Insulinotropic Action of PACAP38 in HIT-T15 Cells

Filipsson, Karin; Karlsson, Sven; Åhrén, Bo

doi:10.1074/jbc.273.49.32602

Cited by 16 publications

(9 citation statements)

References 39 publications

(50 reference statements)

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“…PACAP also increases cytosolic Na + concentration ([Na + ] i ), which was shown to contribute to insulin release [27]. A mechanism that is blocked by a PI3-kinase (PI3-K) inhibitor, wortmanin, was also shown to be related to the PACAP-induced insulin release in HIT cells [23].…”

Section: Effects On Insulin Release and Signaling Mechanisms In -Cellsmentioning

confidence: 99%

PACAP in the Glucose and Energy Homeostasis: Physiological Role and Therapeutic Potential

Nakata¹,

Yada

2007

CPD

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous neuropeptide in the central and peripheral nervous systems. PACAP is also produced by pancreatic islet cells. PACAP regulates the glucose and energy metabolism at multiple processes in several tissues. At postprandial states, PACAP potentiates both insulin release from pancreatic beta-cells and insulin action in adipocytes, contributing to energy storage. At fasting states, PACAP on the one hand promotes feeding behavior by activating neuropeptide Y neurons in the hypothalamic feeding center, arcuate nucleus, and on the other hand stimulates secretion of catecholamine and glucagon and thereby induces lipolysis in adipocytes and glucose output from liver. Thus, PACAP plays an integrative role in the glucose and energy homeostasis. Dysfunction of expression, secretion and/or action of PACAP might be involved in the type 2 diabetes and metabolic syndrome. PACAP receptor subtype-specific agonists and/or antagonists are hopeful therapeutic agents.

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Section: Effects On Insulin Release and Signaling Mechanisms In -Cellsmentioning

confidence: 99%

PACAP in the Glucose and Energy Homeostasis: Physiological Role and Therapeutic Potential

Nakata¹,

Yada

2007

CPD

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“…PACAP has also been shown to open membraneous sodium channels, causing an inward membrane current (83), and studies using fluorophor-labeled clonal cells have displayed an increase in the cytoplasmic sodium concentration after administration of PACAP (85). Furthermore, removal of extracellular sodium impairs the insulinotropic action of PACAP without affecting the formation of cAMP (85), suggesting that the uptake of sodium is involved in PACAP-induced insulin secretion.…”

Section: Intracellular Signaling Mechanismsmentioning

confidence: 99%

Section: Intracellular Signaling Mechanismsmentioning

confidence: 99%

“…Furthermore, removal of extracellular sodium impairs the insulinotropic action of PACAP without affecting the formation of cAMP (85), suggesting that the uptake of sodium is involved in PACAP-induced insulin secretion. The increase in cytoplasmic sodium by PACAP has been shown to be abolished by the PKA inhibitor H89, suggesting that the sodium channel is regulated by cAMP and PKA (85). The influx of sodium might contribute to the opening of the voltagedependent calcium channels through a depolarizing effect, thus increasing cytoplasmic calcium and thereby potentiating insulin secretion (83).…”

Section: Intracellular Signaling Mechanismsmentioning

confidence: 99%

“…The influx of sodium might contribute to the opening of the voltagedependent calcium channels through a depolarizing effect, thus increasing cytoplasmic calcium and thereby potentiating insulin secretion (83). However, PACAP has been shown to increase cytoplasmic calcium in the absence of extracellular sodium (85), suggesting that sodium is also of importance for the events of exocytosis distal to calcium influx. However, this needs further investigation.…”

Section: Intracellular Signaling Mechanismsmentioning

confidence: 99%

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The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

2001

Self Cite

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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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PACAP Is an Islet Neuropeptide Which Contributes to Glucose-Stimulated Insulin Secretion

Filipsson

Sundler

Åhrén

1999

Biochemical and Biophysical Research Communications

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Evidence for Contribution by Increased Cytoplasmic Na+ to the Insulinotropic Action of PACAP38 in HIT-T15 Cells

Cited by 16 publications

References 39 publications

PACAP in the Glucose and Energy Homeostasis: Physiological Role and Therapeutic Potential

PACAP in the Glucose and Energy Homeostasis: Physiological Role and Therapeutic Potential

The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

PACAP Is an Islet Neuropeptide Which Contributes to Glucose-Stimulated Insulin Secretion

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