Effects of D-mannoheptulose and its hexaacetate ester on hormonal secretion from the perfused pancreas.

D-mannoheptulose was recently proposed to be transported into cells by GLUT2, whereas its hexaacetate ester may cross the plasma membrane without requiring the intervention of a specific carrier system. In the light of these proposals, the effects of unesterified D-mannoheptulose and D-mannoheptulose hexaacetate upon hormonal secretion by the perfused rat pancreas were now investigated. Unesterified D-mannoheptulose (1.7 mM) inhibited insulin release and, in most cases, somatostatin output, whereas it augmented glucagon secretion by pancreases exposed to D-glucose (3.3 mM) in the presence of the dimethyl ester of succinic acid (SAD, 10.0 mM). The heptose failed, however, to affect hormonal secretion in the sole presence of SAD. D-mannoheptulose hexaacetate (also 1.7 mM) reproduced, within limits, the effects of unesterified D-mannoheptulose in pancreases exposed to both D-glucose and SAD. In addition, however, the ester displayed a positive effect upon the secretion of the three hormones, even in the sole presence of SAD. These findings support the view that monosaccharide esters may affect the secretion of pancreatic hormones in a dual manner, linked to both the metabolic response to their glucidic moiety and a direct effect of the ester itself. Moreover, they reveal that unesterified D-mannoheptulose is able to antagonize the effect of D-glucose upon hormonal secretion even in cells claimed not to contain GLUT2. The modality by which D-mannoheptulose apparently gains access to the cytosol of these cells remains to be elucidated.