FUNCTIONAL-HETEROGENEITY OF SINGLE PANCREATIC BETA-CELLS STIMULATED BY L-LEUCINE AND THE METHYL-ESTER OF SUCCINIC OR GLUTAMIC-ACID

Single pancreatic beta-cells exposed to D-glucose in the absence or pr esence of L-leucine and to the amino acid in the absence or presence o f either the monomethyl ester of succinic acid (SME) or the dimethyl e ster of glutamic acid (SME) were examined in a reverse hemolytic plaqu e assay for insulin release. At a D-glucose concentration of 11.1 mM, plaque-forming cells amounted to 84.8 +/- 1.0% including 11.4 +/- 4.1% of cells forming large plaques. These percentages were not increased by the incorporation of L-leucine (5 mM) into the incubation medium de spite the fact that the amino acid, when tested in the absence of D-gl ucose, caused sizeable secretory activity. When the secretory response evoked by L-leucine was increased by either SME (10 mM) or GME (3 mM) , marked heterogeneity of individual beta-cells in terms of both the o ccurrence and magnitude of hemolytic plaques was again observed. These findings argue against the view that the heterogeneity in secretory b ehavior of isolated purified beta-cells can be accounted for solely by differences in hexose metabolism as conceivably attributable to indiv idual variations in glucokinase activity. (C) 1995 Academic Press, Inc .