A re-assessment of the role of protein kinase C in glucose-stimulated insulin secretion.
Isolated rat islets of Langerhans which had been pretreated with 200 nM-phorbol 12-myristate 13-acetate (PMA) for 20-24 h, a treatment reported in other cell types to deplete cells of protein kinase C activity, were found not to contain detectable Ca2+/phospholipid-dependent protein kinase activity. These islets did not secrete insulin in response to a subsequent exposure to PMA (0.1 or 1 microM) during a 30 min incubation, although insulin secretion could be stimulated by 20 mM-glucose, a response which was enhanced by 20 microM-forskolin. PMA-pretreated islets that had been permeabilized by high-voltage discharge showed unimpaired secretory responses to an increase in Ca2+ concentration, cyclic AMP and forskolin. These results suggest that (i) pretreatment of islets with tumour-promoting phorbol esters may be a useful means of investigating the role of protein kinase C in stimulus-secretion coupling in the pancreatic beta-cell and (ii) protein kinase C may not play an essential role in glucose-induced insulin secretion.
Hii
C S
CS
Department of Physiology, Kings College London, University of London, U.K.
Jones
P M
PM
Persaud
S J
SJ
Howell
S L
SL
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007328:Insulin; D011506:Proteins; D005576:Colforsin; D013395:Sucrose; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate