EXOGENOUS ARACHIDONIC-ACID INACTIVATES PROTEIN-KINASE-C IN MOUSE PANCREATIC-ISLETS

Citation
P. Thams et al., EXOGENOUS ARACHIDONIC-ACID INACTIVATES PROTEIN-KINASE-C IN MOUSE PANCREATIC-ISLETS, Acta Physiologica Scandinavica, 149(2), 1993, pp. 227-235
Citations number
29
Categorie Soggetti
Physiology
ISSN journal
00016772
Volume
149
Issue
2
Year of publication
1993
Pages
227 - 235
Database
ISI
SICI code
0001-6772(1993)149:2<227:EAIPIM>2.0.ZU;2-K
Abstract
The effect of arachidonic acid on protein kinase C activity and insuli n secretion in mouse islets was investigated. Arachidonic acid stimula ted protein kinase C activity in islet cytosol and membrane fractions by substituting for phosphatidylserine. Stimulation by arachidonic aci d was dependent on either Ca2+ or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate, was potentiated by the combined addition of Ca2+ 12-O-tetradecanoylphorbol 13-acetate, and did not further increase pr otein kinase C activity in the presence of saturating concentrations o f phosphatidylserine. Arachidonic acid stimulation of protein kinase C was prevented by binding of arachidonic acid to albumin. In the absen ce of extracellular Ca2+, exogenous arachidonic acid stimulated insuli n secretion. Arachidonic acid-induced insulin secretion was not potent iated by 12-O-tetradecanoylphorbol 13-acetate and was not prevented by the protein kinase C inhibitor staurosporine, suggesting that arachid onic acid-induced insulin secretion may occur independently of protein kinase C activation. Arachidonic acid-induced insulin secretion in Ca 2+-free medium was on the other hand potentiated by addition of extrac ellular Ca2+. Stimulation of insulin secretion by exogenous arachidoni c acid was associated with inactivation of protein kinase C. Inactivat ion of protein kinase C was also observed in islet homogenate after pr e-incubation with arachidonic acid. Arachidonic acid-induced protein k inase C inactivation in islet homogenate was prevented by albumin or M gATP. Inactivation by arachidonic acid in intact islets was, however, not produced during enzyme isolation and was not prevented by inclusio n of albumin or MgATP during preparation of protein kinase C extracts. In conclusion, it is suggested, that arachidonic acid, by inactivating protein kinase C, may exert toxic effects in islets, and that arachid onic acid may stimulate insulin secretion by a non-physiological mecha nism, possibly involving an ionophoretic effect of arachidonic acid to induce Ca2+-mediated insulin release.