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Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists

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Published in Annals of the New York Academy of Sciences. 1986, vol. 488, p. 317-33
Abstract The initial events in signal transduction in insulin-secreting cells are summarized in FIGURE 8. Both nutrient stimuli, such as glucose and amino acids and the muscarinic agonist carbachol (carbamylcholine) raise [Ca2+]i. Although the rise in [Ca2+]i precedes the stimulation of insulin release, it is not a moment-to-moment regulator of release. The metabolizable fuel stimuli cause Ca2+ influx through voltage-dependent Ca2+ channels following depolarization of the membrane potential. In contrast, carbachol, which does not depolarize, elicits Ptd Ins 4,5-P2 hydrolysis, a reaction catalyzed by phospholipase C. The generation of Ins 1,4,5-P3 in this instance is Ca2+ independent, but appears to involve a GTP-binding protein. However, this protein is not a substrate for pertussis toxin. The levels of Ins 1,4,5-P3, which releases Ca2+ from an ATP-dependent Ca2+ pool of the endoplasmic reticulum, are increased prior to the rise in [Ca2+]i. The mitochondria may take up Ca2+ after large increases in [Ca2+]i. A previously proposed second messenger, arachidonic acid, is much less selective than Ins 1,4,5-P3 in that it releases Ca2+ from mitochondria as well as from the endoplasmic reticulum in a slow and irreversible manner. As Ins 1,4,5-P3 is also generated during glucose stimulation of islets, albeit in a Ca2+-dependent manner, this metabolite could mediate not only the action of carbachol but also contribute to amplifying the [Ca2+]i rise in response to glucose.
Keywords Amino Acids/pharmacologyAnimalsArachidonic AcidArachidonic Acids/metabolismCalcium/metabolismCarbachol/pharmacologyGlucose/pharmacologyGlyceraldehyde/pharmacologyHomeostasisInositol 1,4,5-TrisphosphateInositol Phosphates/biosynthesis/metabolismInsulin/secretionIslets of Langerhans/drug effects/metabolism/secretionMembrane Potentials
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PMID: 3107454
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WOLLHEIM, Claes, BIDEN, Trevor John. Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists. In: Annals of the New York Academy of Sciences, 1986, vol. 488, p. 317-33. https://archive-ouverte.unige.ch/unige:55475

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