Scientific article
Review
English

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

Published inAnnals of the New York Academy of Sciences, vol. 488, p. 317-333
Publication date1986
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/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
Citation (ISO format)
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. 317–333. doi: 10.1111/j.1749-6632.1986.tb54414.x
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Journal ISSN0077-8923
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