Important role of XXXX for the stimulatory action of @entity268 on pancreatic beta-cell exocytosis and release of insulin.

@entity268 @entity2833 @entity35 @entity9608 @entity14888 @entity32237 @entity1919 @entity21253 @entity15212 @entity413
@entity1919 potentiates @entity413 -stimulated insulin release and mediates the stimulatory effects of hormones such as @entity15212 ( @entity15212 ) on pancreatic beta-cells. By inhibition of @entity268 -degrading phosphodiesterase (PDE) and, in particular, selective inhibition of @entity14888 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on beta-cell @entity14888 is, however, scarce. To provide such information, we have studied the specific effects of the @entity21253 isoform by adenovirus-mediated overexpression. In @entity35 islets and @entity35 @entity9608 cells, approximate 10-fold overexpression of @entity21253 was accompanied by a 6-8-fold increase in membrane-associated @entity21253 activity. The @entity268 concentration was significantly lowered in transduced cells ( @entity2833 (832/13)), and insulin secretion in response to stimulation with high @entity413 (11.1 mm) was reduced by 40% (islets) and 50% ( @entity2833 ). Further, the ability of @entity15212 (100 nm) to augment @entity413 -stimulated insulin secretion was inhibited by approximately 30% (islets) and 70% ( @entity2833 ). Accordingly, when stimulating with @entity268 , a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single beta-cells. In untransduced @entity9608 cells, application of the @entity14888 -selective inhibitor @entity32237 (10 microm) was shown to increase @entity413 -stimulated insulin release as well as @entity268 -enhanced exocytosis. The findings suggest a significant role of @entity21253 as an important regulator of insulin secretory processes.
