Insulinotropic action of alpha-D-glucose pentaacetate in vivo

The insulinotropic action of alpha-D-glucose pentaacetate (GPA) was explored in vivo. In fed anaesthetized rats, as little as 8.5 nmol GPA per g body wt., given intravenously, was sufficient to cause a modest, but highly significant, biphasic increase in plasma insulin concentration, At the same low dosage, GPA, whilst failing to affect the early increase in insulinaemia caused by the intravenous injection of either gliquidone (0.2 nmol/g body wt.) or repaglinide (0.1 nmol/g body wt.), enhanced or prolonged the insulinotropic action of these antidiabetic agents beyond the 10th min after their administration, When given orally to conscious rats, GPA tested in amounts 3-4 times higher than those used in the preceding experiments, failed to stimulate insulin release and was even unable to prevent the fall in plasma insulin concentration otherwise caused by the handling and bleeding of conscious animals, suggesting a negligible absorption of the ester from the gastrointestinal tract into the bloodstream, The circulating concentration of GPA reached shortly after its intravenous injection not exceeding a theoretical value close to 0.04 mM, the present findings document the exquisite sensitivity of the B-cell to this new secretagogue, that could conceivably be used to bypass a deficiency of the hexose-carrier system currently incriminated as a factor of B-cell dysfunction in non-insulin dependent diabetes mellitus. (C) 1997, Editrice Kurtis.