Ontogeny and Species Differences in the Pancreatic Expression and Localization of the CCKA Receptors

Bourassa, Judith; Lainé, Jean; Kruse, Marie‐Luise; Gagnon, Marie‐Claude; Calvo, Ézéquiel; Morisset, Jean

doi:10.1006/bbrc.1999.0988

Cited by 55 publications

(32 citation statements)

References 28 publications

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“…In contrast to previous studies performed in isolated rat islets (52-54), our study did not reveal facilitation of insulin secretion in response to cholecystokinin-8, which might be partly due to species-specific differences in gene expression: The cholecystokinin receptor CCK-A has been shown to be highly expressed in rat islets (55), while expression in murine islets is -according to our own analyses (data not shown) and published data -weak to undetectable (19,46,56). However, a mild facilitating effect of CCK at 8.3 mM glucose has been described by others (57), and we therefore hypothesize that CCK mediates a weak facilitation at low to intermediate glucose levels, which is masked by the high glucose concentrations used in our experiments.…”

Section: Discussioncontrasting

confidence: 99%

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

Sassmann¹,

Gier²,

Gröne³

et al. 2010

J. Clin. Invest.

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A variety of neurotransmitters, gastrointestinal hormones, and metabolic signals are known to potentiate insulin secretion through GPCRs. We show here that β cell-specific inactivation of the genes encoding the G protein α-subunits Gα q and Gα 11 resulted in impaired glucose tolerance and insulin secretion in mice. Interestingly, the defects observed in Gα q /Gα 11 -deficient β cells were not restricted to loss of muscarinic or metabolic potentiation of insulin release; the response to glucose per se was also diminished. Electrophysiological recordings revealed that glucose-induced depolarization of isolated β cells was impaired in the absence of Gα q /Gα 11 , and closure of K ATP channels was inhibited. We provide evidence that this reduced excitability was due to a loss of β cell-autonomous potentiation of insulin secretion through factors cosecreted with insulin. We identified as autocrine mediators involved in this process extracellular nucleotides such as uridine diphosphate acting through the G q /G 11 -coupled P2Y6 receptor and extracellular calcium acting through the calciumsensing receptor. Thus, the G q /G 11 -mediated signaling pathway potentiates insulin secretion in response to glucose by integrating systemic as well as autocrine/paracrine mediators. IntroductionThe adequate secretion of insulin from pancreatic β cells is essential for the maintenance of normoglycemia; impaired insulin secretion results in diabetes mellitus with hyperglycemia, dyslipidemia, and consequent long-term tissue damage (1). The on-demand release of insulin from β cells is mainly regulated by blood glucose levels: high concentrations of glucose result in enhanced intracellular glucose metabolism with accumulation of ATP and consecutive closure of ATP-sensitive K + channels, leading to the opening of voltage-operated Ca 2+ channels and Ca 2+ -mediated exocytosis of insulin-containing vesicles (2, 3).While the ATP-dependent mechanism is clearly the master regulator of insulin release, various mediators potentiate insulin release in response to glucose. For example, gastrointestinal hormones such as glucose-dependent insulinotropic polypeptide (GIP) or glucagon-like peptide-1 (GLP-1) potentiate insulin secretion by activation of GPCRs, which signal through the G s family of heterotrimeric G proteins (4-6). The potentiating effect of G s on glucose-induced insulin release depends on activation of adenylyl cyclase and consecutive phosphorylation of voltage-operated Ca 2+ channels (7, 8) or opening of nonselective cation channels (9).Another important group of modulators are neurotransmitters and neuropeptides (10, 11), most prominent among them being the neurotransmitter acetylcholine, which is released from vagal nerve terminals and potentiates insulin secretion through the muscarinic receptor subtype M 3 (12)(13)(14)(15). In contrast to the receptors for GIP and GLP-1, the M 3 receptor does not elicit G smediated adenylyl cyclase activation, but was shown to signal through the G q /G 11 family of heterotrimeric G proteins. Th...

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Section: Discussioncontrasting

confidence: 99%

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

Sassmann¹,

Gier²,

Gröne³

et al. 2010

J. Clin. Invest.

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“…The selective localization of CCK1 receptors in acinar cells holds true in the pancreas of other mammals, including the guinea pig and rat ( Supplementary Figure-4). In agreement with the current study, two previous immunohistochemical studies for the CCK1 receptor have reported a positive immunoreaction in the plasma membrane of pancreatic acinar cells in the mouse and rat (Bourassa et al 1999;Ohlsson et al 2000). Unlike our investigation, however, those studies simultaneously detected the immunoreaction for CCK1 receptors in pancreatic islets.…”

Section: Cck1 Receptor In Pancreatic Acinar Cellssupporting

confidence: 93%

“…However, findings have been inconsistent for the expression sites-even in the pancreas. Some histochemical studies reported the localization of CCK1 receptors in acinar cells of the pancreas (Bourassa et al 1999;Ohlsson et al 2000), while other histochemical studies of the pancreas documented the localization of CCK1 receptors in islet cells in the pancreas of several mammalian species (Kageyama et al 2005;Karlsson et al 1998;Morisset et al 2003;Schweiger et al 2000); some of these appeared to detect no immunoreactivity for CCK1 receptors in acinar cells. Cell types of islets expressing the CCK1 receptor are also controversial among researchers, possibly due to species difference, varied immunohistochemical procedures, and the specificity of the antisera used.…”

Section: Introductionmentioning

confidence: 99%

Cellular and subcellular localization of cholecystokinin (CCK)-1 receptors in the pancreas, gallbladder, and stomach of mice

Konno

Takahashi-Iwanaga

Uchigashima

et al. 2014

Histochem Cell Biol

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“…Imoto et al [12] and Mineo et al [17] reported that normal growth of both acinar and islet cells were inhibited in rats and sheep by administration of CCK-RA. Expression of mRNA coding CCK-A receptor was also reported not only in acinar cells but also in beta cells [2]. Our study demonstrated that plasma CCK concentration was reduced by only 10% after CCK-RA administration.…”

Section: Role Of Cck In the Regeneration Of Remnant Pancreassupporting

confidence: 63%

Effect of Cholecystokinin-A Receptor Antagonist on Rat Pancreas after Partial Pancreatectomy

Handa

Suzuki

Hayashi

et al. 2004

Acta Histochem. Cytochem

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Ontogeny and Species Differences in the Pancreatic Expression and Localization of the CCKA Receptors

Cited by 55 publications

References 28 publications

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

Cellular and subcellular localization of cholecystokinin (CCK)-1 receptors in the pancreas, gallbladder, and stomach of mice

Effect of Cholecystokinin-A Receptor Antagonist on Rat Pancreas after Partial Pancreatectomy

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