DUAL-MODE OF ACTION OF GLUCOSE PENTAACETATES ON HORMONAL SECRETION FROM THE ISOLATED-PERFUSED RAT PANCREAS

Isolated perfused rat pancreases were exposed, in the presence of 10.0 mM L-leucine, to either alpha-D-glucose pentaacetate, beta-L-glucose pentaacetate, or unesterified D-glucose, all tested at a 1.7 mM concen tration. The pentaacetate ester of alpha-D-glucose and, to a lesser ex tent, that of beta-L-glucose stimulated both insulin and somatostatin release, whereas unesterified D-glucose failed to do so. In the case o f insulin output, the two eaters differed from one another not solely by the magnitude of the secretory response but also by its time course and reversibility. Compared with these data, the most salient differe nce found in the case of somatostatin release consisted of the absence of an early secretory peak in response to alpha-D-glucose pentaacetat e administration and the higher paired ratio between the secretory res ponses evoked by the esters of glucose and by unesterified D-glucose ( 5.5 mM) administered at the end of the experiments. The two eaters pro voked an initial and short-lived stimulation of glucagon secretion, in sharp contrast to the immediate inhibitory action of unesterified D-g lucose. Thereafter, alpha-D-glucose pentaacetate, but not beta-L gluco se pentaacetate, caused inhibition of glucagon release, such an effect being reversed when the administration of the ester was halted. These findings indicate a dual mode of action of glucose pentaacetate ester s on hormonal secretion from the endocrine pancreas. The intracellular hydrolysis of alpha-D-glucose pentaacetate and subsequent catabolism of its hexose moiety may contribute to the early peak-shaped insulin r esponse to this ester, to the persistence of a positive secretory effe ct in B and D cells after cessation of its administration, and to the late inhibition of glucagon release. However, a direct effect of the e aters themselves, by some as-of-yet unidentified coupling process, is postulated to account for the stimulation of insulin and somatostatin release by beta-L-glucose pentaacetate and for the initial enhancement of glucagon secretion provoked by both glucose esters.