The p38 mitogen-activated protein kinase cascade is not required for the stimulation of insulin secretion from rat islets of Langerhans.
The expression of the p38 subfamily of mitogen-activated protein kinases (MAPKs) was examined in rat islets of Langerhans and pancreatic beta-cell lines, and its involvement in the regulation of insulin secretion was investigated. Rat islets and several rodent beta-cell lines were shown to express p38 MAPK by Western blotting. The cellular stress agents sodium arsenite and hyperosmotic sorbitol significantly stimulated p38 MAPK activity, as did the tyrosine phosphatase inhibitor sodium pervanadate and the serine/threonine phosphatase inhibitor okadaic acid. Increases in p38 MAPK activity were not consistently correlated with increases in insulin secretion, and the dissociation between p38 MAPK activity and the regulation of insulin secretion was further demonstrated in studies using the specific p38 MAPK inhibitor SB203580, which was without significant effect on the stimulation of insulin secretion by glucose, 4beta phorbol myristate acetate and forskolin. These studies indicate that although p38 MAPK is expressed in pancreatic beta-cells and can be activated pharmacologically, its activity can be dissociated from the exocytotic release of insulin from rat islets of Langerhans.
Burns
C J
CJ
Endocrinology and Reproduction Research Group, School of Biomedical Sciences, Kings College London, UK. chris.burns@kcl.ac.uk
Howell
S L
SL
Jones
P M
PM
Persaud
S J
SJ
D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006706:Homeostasis; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D017670:Sodium Compounds / Q000494:pharmacology; D013012:Sorbitol / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D018053:Arsenites; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007328:Insulin; D011725:Pyridines; D017670:Sodium Compounds; C076715:pervanadate; D005576:Colforsin; D019319:Okadaic Acid; D014638:Vanadates; C017947:sodium arsenite; D013012:Sorbitol; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; C093642:SB 203580