Glucose-stimulated insulin secretion from rat islets of Langerhans is independent of mitogen-activated protein kinase activation

The role played by mitogen-activated protein kinases (MAPKs) in the regulation of insulin secretion from adult rat islets of Langerhans was investigated by examining the effects of glucose, forskolin and 4 beta phorbol myristate acetate (PMA) on islet MAPK activity and by measuring insulin secretion from islets in response to these agonists after inhibition of MAPK by PD 098059 (PD). Glucose (20mM) had a small (<2-fold) stimulatory effect on MAPK activity in isolated islets, and this was potentiated by forskolin (10 mu M) and PMA (500nM), which also significantly stimulated MAPK activity at 2mM glucose. Pretreatment of islets with 50 mu M PD inhibited MAPK activity, but had no effect on secretory responses to glucose, forskolin and PMA. These results suggest that although MAPK may be activated by insulin secretagogues in adult rodent islets, this can be dissociated from the exocytotic release of insulin. (C) 1997 Academic Press.