GLUCOSE-STIMULATED INSULIN-SECRETION FROM RAT ISLETS OF LANGERHANS ISINDEPENDENT OF MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION

The role played by mitogen-activated protein kinases (MAPKs) in the re gulation 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 measuri ng insulin secretion from islets in response to these agonists after i nhibition of MAPK by PD 098059 (PD). Glucose (20mM) had a small (<2-fo ld) stimulatory effect on MAPK activity in isolated islets, and this w as potentiated by forskolin (10 mu M) and PMA (500nM), which also sign ificantly stimulated MAPK activity at 2mM glucose. Pretreatment of isl ets with 50 mu M PD inhibited MAPK activity, but had no effect on secr etory responses to glucose, forskolin and PMA. These results suggest t hat although MAPK may be activated by insulin secretagogues in adult r odent islets, this can be dissociated from the exocytotic release of i nsulin. (C) 1997 Academic Press.