Inhibitory action of the anomers of 2-deoxy-D-glucose tetraacetate on the metabolism of D-glucose in rat pancreatic islets.

Background: The tetra-acetate ester of 2-deoxy-D-glucose was recently found to either inhibit or augment insulin secretion, depending on the concentration of the ester. Both the positive and negative insulinotropic actions of the ester display anomeric specificity.

Methods: The effects of the alpha- and beta-anomer of 2-deoxy-D-glucose tetra-acetate (5.

Effects of the methyl esters of pyruvate, succinate and glutamate on the secretory response to meglitinide analogues in rat pancreatic islets.

The insulinotropic action of the meglitinide analogues KAD-1229, A-4166 and repaglinide was examined in rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of nutrient secretagogues such as D-glucose and the methyl esters of pyruvic acid, succinic acid and glutamic acid. The meglitinide analogues exerted little effect on insulin release in the absence of exogenous nutrient or in the presence of methyl pyruvate. They caused obvious stimulation of insulin output in the presence of D-glucose, dimethyl succinate or dimethyl glutamate.

Ionophoretic properties of the non-sulfonylurea hypoglycemic agents A-4166 and KAD-1229.

The non-sulphonylurea hypoglycaemic agents A-4166 and KAD-1229 were both found to cause 45Ca or 22Na translocation from an aqueous medium into an organic immiscible phase. This ionophoretic effect was more marked with A-4166 than KAD-1229, in mirror image of their insulinotropic potency. Such a dissociated behaviour argues against the view that the ionophoretic properties of these agents represent a major determinant of their insulinotropic action.

Insulinotropic response to enterally administered succinic and glutamic acid methyl esters.

Both the monomethyl and dimethyl esters of succinic acid, administered enterally to fasted rats, caused a rapid increase in plasma insulin. Such was not the case, however, after enteral administration of either succinic acid or the dimethyl ester of glutamic acid. The time course for the appearance of radioactive material in plasma was also vastly different after enteral administration of either [1,4-14C]succinic acid or its dimethyl ester.

Insulinotropic action of meglitinide analogs: concentration-response relationship and nutrient dependency.

The insulinotropic action of meglitinide was compared to that of its analogs S 3075, A-4166, KAD-1229 and repaglinide. None of these hypoglycemic agents significantly enhanced insulin output from rat pancreatic islets incubated for 90 min in the absence of exogenous nutrient. However, all these agents, when tested at a 10 microM concentration, augmented insulin release evoked by either 7 mM D-glucose or 10 microM succinic acid monomethyl ester (SAM).