The cyclic AMP-protein kinase A pathway restrains islet phospholipase A(2) activation.
Although phospholipase A(2) (PLA(2)) is of importance for insulin secretion, it is not established how it relates to other signalling mechanisms. This study examined the crosstalk between PLA(2) and the cyclic AMP (cAMP)-protein kinase A (PKA) pathway in isolated rat islets. Forskolin, IBMX, and dbcAMP reduced [(3)H]arachidonic acid ([(3)H]AA) efflux from prelabelled islets during PLA(2) activation by mellitin or cholecystokinin (CCK-8), while efflux induced by carbachol was unaffected. The PKA inhibitor myrPKI(14-22) prevented this reduction of CCK-8-induced efflux. Glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and vasoactive intestinal polypeptide (VIP) diminished CCK-8-induced efflux. Also in the absence of Ca(2+), forskolin/IBMX and dbcAMP reduced CCK-8-induced efflux. In parallel with effects on [(3)H]AA, the expected additive insulin secretion induced by mellitin or CCK-8 in combination with forskolin or GLP-1, respectively, was reduced. In conclusion, the cAMP-PKA pathway restrains both Ca(2+)-dependent and Ca(2+)-independent PLA(2) activation, indicating a regulating crosstalk between these two pathways.
Simonsson
E
E
Wallenberg Laboratory, Department of Medicine, Lund University, University Hospital of Malmö, Malmö, SE-205 02, Sweden. erik.simonsson@medforsk.mas.lu.se
Karlsson
S
S
Ahrén
B
B
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008555:Melitten / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012844:Sincalide / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D005576:Colforsin; D008555:Melitten; D014660:Vasoactive Intestinal Peptide; D005749:Gastric Inhibitory Polypeptide; D003994:Bucladesine; D052216:Glucagon-Like Peptide 1; D002217:Carbachol; D005934:Glucagon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010741:Phospholipases A; D012844:Sincalide; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine