Stimulatory Effects of Prostaglandins E-l, E-2, and F-2-Alpha on Glucagon and Insulin Release In Vitro

Abstract

The effects of prostaglandins (PG) E₁, E₂, and F₂ upon the release of glucagon and insulin from the isolated perfused rat pancreas were investigated. In the presence of 5.6 mM glucose the release of both glucagon and insulin was stimulated by PGF₂α at several concentrations ranging from 2.8 × 10⁻⁸ M to 3.6 × 10⁻⁶ M. Ten-minute perfusions of 1.4 × 10⁻⁶ M PGE₁ or 2.8 × 10⁻⁷ M PGF₂α evoked biphasic release of both islet hormones, and they augmented their biphasic release induced by 10 mM L-arginine. The addition of 5 mM fumarate, glutamate, and pyruvate permitted PGE₂ to stimulate insulin release at a concentration as low as 1.1 × 10⁻⁹ M. The failure of 10⁻⁶ M oleic acid to elicit hormone release suggested that these effects of PGs were not nonspecific effects of long-chain fatty acids. In the absence of glucose, in response to 2.8 × 10⁻⁷ M PGE₁ or PGE₂ or PGF₂α, the magnitudes of glucagon release were similar to or slightly greater than those seen with 5.6 mM D-glucose, but the release of insulin failed to occur. In the presence of 16.7 mM glucose, in response to 1.4 × 10⁻⁶ M PGE₂ and 2.8 × 10⁻⁷ M PGF₂α, the release of glucagon was blunted and that of insulin unchanged as compared with the secretory responses seen in the presence of 5.6 mM D-glucose. These data indicate that administered PG_s can stimulate acutely the release of glucagon and insulin at pharmacologic concentrations as well as at concentrations similar to those found in pancreatic tissues and effluent. These observations are in keeping with the hypothesis that PG_s of the E and F series may play a role in the regulation of secretion of glucagon and insulin.