Influence of D-glucose upon the respiratory and secretory response of insulin-producing tumor cells to 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid.

In insulin-producing cells of the RINm5F line, the nonmetabolized analogue of L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid decreases O2 consumption, lowers ATP content, and inhibits insulin release despite stimulation of both NH4 production and 14CO2 output from cells prelabeled with L-[U-14C]glutamine. The metabolic and secretory effects of 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid are opposed to those of D-glucose, which increases respiration, ATP content, and insulin release, while lowering NH4+ production and 14CO2 output from the prelabeled cells. D-Glucose also antagonizes the inhibitory action of 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid upon both respiration and secretion. These findings suggest that, in tumor as in normal islet cells, the regulation of insulin release by exogenous nutrients depends on the availability of endogenous ATP.