Atypical isoforms of pKc and insulin secretion from pancreatic beta-cells: evidence using Gö 6976 and Ro 31-8220 as Pkc inhibitors.
The involvement of protein kinase C (PKC) isoforms in glucose-induced insulin secretion was investigated by comparing the effects of the PKC inhibitors Gö 6976, which is PKC specific and selective for the Ca(2+)-dependent isoforms, and Ro 31-8220, a specific PKC inhibitor which does not discriminate between isoforms. Gö 6976 inhibited the Ca(2+)- and diacylglycerol (DAG)-dependent PKC activities in beta-cell extracts in vitro and fully inhibited insulin secretory responses of rat islets of Langerhans to the PKC activator 4 beta phorbol myristate acetate (PMA), suggesting that it was an effective inhibitor of the DAG-dependent isoforms of PKC in situ. However, glucose-induced insulin secretion from rat islets was not inhibited by Gö 6976, whereas secretory responses to glucose were partially inhibited by the non-isoform selective PKC inhibitor, Ro 31-8220. The simplest explanation of these results is that glucose-induced insulin secretion is dependent, at least in part, upon the activation of an atypical isoform(s) of PKC within the beta-cell.
Harris
T E
TE
Biomedical Sciences Division, King's College London, United Kingdom.
Persaud
S J
SJ
Jones
P M
PM
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D007527:Isoenzymes; C081021:Go 6976; D011493:Protein Kinase C; D005947:Glucose; C064758:Ro 31-8220