Glucose-stimulated insulin secretion is not dependent on activation of protein kinase A.
The involvement of cyclic AMP-dependent protein kinase A (PKA) in the exocytotic release of insulin from rat pancreatic islets was investigated using the Rp isomer of adenosine 3',5'-cyclic phosphorothioate (Rp-cAMPS). Preincubation of electrically permeabilised islets with Rp-cAMPS (1 mM, 1 h, 4 degrees C) inhibited cAMP-induced phosphorylation of islet proteins of apparent molecular weights in the range 20-90 kDa, but did not affect basal (50 nM Ca2+) nor Ca2(+)-stimulated (10 microM) protein phosphorylation. Similarly, Rp-cAMPS (500 microM) inhibited both cAMP- (100 microM) and 8BrcAMP-induced (100 microM) insulin secretion from electrically permeabilised islets without affecting Ca2(+)-stimulated (10 microM) insulin release. In intact islets, Rp-cAMPS (500 microM) inhibited forskolin (1 microM, 10 microM) potentiation of insulin secretion, but did not significantly impair the insulin secretory response to a range of glucose concentrations (2-20 mM). These results suggest that cAMP-induced activation of PKA is not essential for either basal or glucose-stimulated insulin secretion from rat islets.
Persaud
S J
SJ
Biomedical Sciences Division, King's College London, Kensington, U.K.
Jones
P M
PM
Howell
S L
SL
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013873:Thionucleotides / Q000494:pharmacology*
D007328:Insulin; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D011494:Protein Kinases; D005947:Glucose; D002118:Calcium