Role of protein kinase C in arginine-induced glucagon secretion from isolated rat islets of Langerhans.
This study investigated the effect of pretreatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA) on arginine-induced glucagon secretion. Isolated islets of Langerhans were pretreated by culturing for 18-24 h in the presence of 200 nM of the tumour-promoting phorbol ester PMA or 200 nM of the non-tumour-promoting phorbol ester 4-phorbol didecanoate (PDD). Islets pretreated with PMA did not secrete glucagon in response to 0.1 or 1 microM PMA on subsequent incubation, in contrast to PDD-pretreated islets which responded significantly on subsequent incubation with PMA. Pretreatment with PMA led to impairment of arginine-induced glucagon secretion. PMA-pretreated islets permeabilized by high-voltage discharge retained their normal secretory responses to calcium and cyclic AMP, but had an impaired secretory response to PMA. These results suggest (1) that protein kinase C (PKC) is likely to be present in the A cell, (2) that short-term culture in tumour-promoting phorbol ester leads to down-regulation of PKC, (3) that the PKC pathway is involved in arginine-induced glucagon secretion and (4) that pretreatment does not effect the A cell response to other intracellular mediators.
Bjaaland
T
T
Department of Physiology, King's College London, University of London.
Hii
C S
CS
Jones
P M
PM
Howell
S L
SL
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000493:pharmacokinetics; D005934:Glucagon / Q000032:analysis / Q000378:metabolism*; D007801:Langerhans Cells / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000493:pharmacokinetics
D005934:Glucagon; D001120:Arginine; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium