Characteristics of phosphoinositide-specific phospholipase C activity from mouse pancreatic islets

Hedeskov, C. J.; Thams, Peter; Gembal, M; Malik, Tariq A.; Capito, Kirsten

doi:10.1016/0303-7207(91)90122-9

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…It has long been known that glucose can stimulate IP production in pancreatic islets (67,68), but neither we nor others (69) have found evidence for an involvement of a glucose-activated plasma membrane receptor. Instead, it was suggested that the glucose-induced phosphoinositide response might be triggered by the accompanying increase in calcium influx (70,71). Our data, however, show that glucose-induced production of IP 3 depends on Gα q /Gα 11 , which led us to the hypothesis that mediators cosecreted with insulin might activate Gα q /Gα 11 and potentiate insulin release in an autocrine feedback loop.…”

Section: Discussioncontrasting

confidence: 54%

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: 54%

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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“…This is evident from the fact that during depolarization, the steady- ] i activate PI-PLC, leading to generation of Ins(1,4,5)P 3 , which by itself activates IP 3 Rs, causing a further increase in [Ca 2ϩ ] i . This view originates from the facts that a minimal level of Ca 2ϩ is essential for activation of PI-PLC (27,28) and that Ca 2ϩ increases PI-PLC activity in mouse islet homogenates (28). In this view, an increase in the concentration of Ins(1,4,5)P 3 (as opposed to an increase in [Ca 2ϩ ]) is the predominant mechanism that couples Ca 2ϩ entry to Ca 2ϩ release.…”

Section: Discussionmentioning

confidence: 99%

Ca2+-induced Ca2+ Release from the Endoplasmic Reticulum Amplifies the Ca2+ Signal Mediated by Activation of Voltage-gated L-type Ca2+ Channels in Pancreatic β-Cells

Lemmens

Larsson

Berggren

et al. 2001

Journal of Biological Chemistry

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“…The activity of a 3500 fold purified human lymphoblastic N-acetylglucosamine-1-phosphotransferase was inhibited by PtdSer, Ptdglycerol and PtdA [17]. The PtdIns specific PLC activity of pancreatic islet cells was inhibited by PtdSer [18]. A soluble PtdA phosphohydrolase from rat liver was inhibited by Ptdglycerol, PtdSer and PtdIns [19].…”

Section: Discussionmentioning

confidence: 99%

Acidic phospholipids inhibit the phospholipase D activity of rat brain neuronal nuclei

et al. 1996

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An oleate dependent form of phospholipase D is present in rat brain neuronal nuclei and both the hydrolytic and transphosphatidylation activities measured. Several acidic phospholipids were found to inhibit this activity in a dose dependent manner. The IC5o values varied from 3.5 ttM for PIP2 to 200 pM for phosphatidic acid. The hydrolysis of PIP2 by phospholipase C would be expected to result in the disinhibition of the oleate dependent phospholipase D activity.

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Characteristics of phosphoinositide-specific phospholipase C activity from mouse pancreatic islets

Cited by 15 publications

References 36 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

Ca2+-induced Ca2+ Release from the Endoplasmic Reticulum Amplifies the Ca2+ Signal Mediated by Activation of Voltage-gated L-type Ca2+ Channels in Pancreatic β-Cells

Acidic phospholipids inhibit the phospholipase D activity of rat brain neuronal nuclei

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