Potentiation of stimulus-induced insulin secretion in protein kinase C-deficient RINm5F cells

Détails

ID Serval
serval:BIB_6F56BBCCD434
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Potentiation of stimulus-induced insulin secretion in protein kinase C-deficient RINm5F cells
Périodique
Biochemical Journal
Auteur(s)
Li  G. D., Regazzi  R., Ullrich  S., Pralong  W. F., Wollheim  C. B.
ISSN
0264-6021 (Print)
Statut éditorial
Publié
Date de publication
12/1990
Volume
272
Numéro
3
Pages
637-45
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 15
Résumé
The role of protein kinase C (PKC) in stimulus recognition and insulin secretion was investigated after long-term (24 h) treatment of RINm5F cells with phorbol 12-myristate 13-acetate (PMA). Three methods revealed that PKC was no longer detectable, and PMA-induced insulin secretion was abolished. Such PKC-deficient cells displayed enhanced insulin secretion (2-6-fold) in response to vasopressin and carbachol (activating phospholipase C) as well as to D-glyceraldehyde and alanine (promoting membrane depolarization and voltage-gated Ca2+ influx). Insulin release stimulated by 1-oleoyl-2-acetylglycerol (OAG) was also greater in PKC-deficient cells. OAG caused membrane depolarization and raised the cytosolic Ca2+ concentration ([Ca2+]i), both of which were unaffected by PKC down-regulation. Except for that caused by vasopressin, the secretagogue-induced [Ca2+]i elevations were similar in control and PKC-depleted cells. The [Ca2+]i rise evoked by vasopressin was enhanced during the early phase (observed both in cell suspensions and at the single cell level) and the stimulation of diacylglycerol production was also augmented. These findings suggest more efficient activation of phospholipase C by vasopressin after PKC depletion. Electrically permeabilized cells were used to test whether the release process is facilitated after long-term PMA treatment. PKC deficiency was associated with only slightly increased responsiveness to half-maximally (2 microM) but not to maximally stimulatory Ca2+ concentrations. At 2 microM-Ca2+ vasopressin caused secretion, which was also augmented by PMA pretreatment. The difference between intact and permeabilized cells could indicate the loss in the latter of soluble factors which mediate the enhanced secretory responses. However, changes in cyclic AMP production could not explain the difference. These results demonstrate that PKC not only exerts inhibitory influences on the coupling of receptors to phospholipase C but also interferes with more distal steps implicated in insulin secretion.
Mots-clé
Alanine/pharmacology Animals Arginine Vasopressin/pharmacology Calcium/metabolism Carbachol/pharmacology Cell Line Cell Membrane/enzymology Cyclic AMP/metabolism Cytosol/enzymology Diglycerides/metabolism/pharmacology Electric Stimulation Glyceraldehyde/pharmacology Insulin/*secretion Kinetics Protein Kinase C/deficiency/*metabolism Signal Transduction Tetradecanoylphorbol Acetate/*pharmacology
Pubmed
Web of science
Création de la notice
24/01/2008 14:30
Dernière modification de la notice
20/08/2019 14:28
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