This article examines the effects of PGE and drugs that inhibit PGE synthesis on pancreatic islet function and glucose homeostasis in vitro and in vivo. It is divided into four sections: insulin secretion; glucagon secretion; glucose tolerance and glucose production; and diabetes mellitus in humans. Of all of the arachidonic acid metabolites so far examined, PGE appears to be the one most likely to have direct effects on pancreatic islet beta cell function. It remains controversial whether PGE is a stimulator or an inhibitor of insulin secretion. However, the weight of the evidence appears to favor an inhibitory role for PGE when one considers all of the in vitro and in vivo data. The interesting in vitro observation that PGE can have stimulatory effects at normal glucose concentrations but inhibitory effects at high glucose concentrations may be an important clue to the resolution of this problem. This raises the possibility that the main physiologic role for PGE in the pancreatic islet is to negatively modulate glucose-stimulated insulin release and, in that sense, counterbalance the positive modulatory actions of c-AMP. The stimulation of insulin release that has been observed in vitro may reflect adenylate cyclase stimulation. If this is so, one might further postulate that PGE is a weak agonist of beta cell adenylate cyclase that interferes with stimulation of c-AMP generation by stronger agonists. Demonstration that this putative weak agonist effect on adenylate cyclase is masked by a stronger inhibitory effect on insulin secretion when the beta cell is exposed to high glucose concentrations will be necessary to resolve the conflicting data thus far reported.
|Original language||English (US)|
|Number of pages||13|
|Journal||Medical Clinics of North America|
|State||Published - Jan 1 1981|