Prostaglandins and the alpha-cell.

Experimental evidence has recently accumulated indicating that administration of some prostaglandins (PGs), particularly those of the E series, can evoke release of glucagon by the pancreatic alpha-cells. Virtually, all the in vitro studies (isolated perfused rat pancreas, isolated guinea-pig islets) agree that PGs can increase both basal and stimulated glucagon release. On the other hand, inhibition of PG synthesis with indomethacin blocks glucagon release. In rats and in normal humans, PGE1, but not PGA2 or PGF2a, causes a progressive rise of plasma glucagon levels. While in the rat this response seems independent of the adrenergic nervous system, in man the hyperglucagonemia induced by PGE1 is easily suppressed by propranolol, suggesting an interaction between the prostaglandin and the beta-receptors of the alpha-cell. Studies with inhibitors of PG synthesis in vivo have yielded conflicting results, depending on the particular experimental protocol used and on the type of inhibitor tested. In normal humans, it seems that acetylsalicylic acid (ASA) has no effect on glucagon response to arginine, tolbutamide and insulin-induced hypoglycemia. Conversely, a stimulator of PG synthesis, such as furosemide, increases glucagon response to an arginine pulse in man. In insulin-dependent diabetics, who present an exaggerated glucagon response to stimulants, ASA fails to alter glucagon response to arginine, but completely blunts the glucagon response to salbutamol, a weak beta-2 receptor agonist. In conclusion, these observations provide evidence in support to a role for PGs, at least PGE, in the contro of glucagon release.