Dominance of cyclooxygenase-2 in the regulation of pancreatic islet prostaglandin synthesis

Dramatic, scientifically important discoveries in prostaglandin (PG) pharmacology and physiology have taken place over the past decade. Chief among these discoveries is the identification of two separate forms of cyclooxygenase (COX), a constitutive and an inducible form, both of which exist in most tissues. The pancreatic islet is an exception to this rule because it continually and dominantly expresses the inducible form, COX-2. It has also been learned that nonsteroidal antiinflammatory drugs affect the two forms of COX with different potencies, a finding with far-reaching clinical implications. An equally important finding is that PGE(2), which is known to negatively modulate glucose-induced insulin secretion, has at least four different subtypes of receptors with different mechanisms of action and metabolic consequences. These recent changes in our understanding of the molecular regulation of PG synthesis call for a reconsideration of previous hypotheses involving PGE(2) as a regulator of beta-cell function in physiological and pathophysiological states.