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

Article Article scientifique Revue de la littérature Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists eng 1986 author Wollheim Claes 25195 author Biden Trevor John 33897 317-333 10.1111/j.1749-6632.1986.tb54414.x 3107454 0077-8923 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. Amino Acids/pharmacology Animals Arachidonic Acid Arachidonic Acids/metabolism Calcium/metabolism Carbachol/pharmacology Glucose/pharmacology Glyceraldehyde/pharmacology Homeostasis Inositol 1,4,5-Trisphosphate Inositol Phosphates/biosynthesis/metabolism Insulin/secretion Islets of Langerhans/drug effects/metabolism/secretion Membrane Potentials Dewey 612 134 Département de physiologie cellulaire et métabolisme 21C false Annals of the New York Academy of Sciences 488 48d98b68-65be-4dc7-8819-b032a20e9bcb Article (Published version) Restricted WOLLHEIM_et_al-1986-Annals_of_the_New_York_Academy_of_Sciences.pdf 976983 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists	Annals of the New York Academy of Sciences			1986	472	0

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Biden, Trevor John