AMINO-ACID RESPONSIVENESS IN BETA-CELL SUBPOPULATIONS WITH DIFFERENT SENSITIVITY TO GLUCOSE

Isolated rat beta-cells differ in their individual responsiveness to g lucose. The present study examines whether two beta-cell subpopulation s with different thresholds for glucose stimulation also differ in the ir responsiveness to amino acids that are known to stimulate insulin r elease. The subpopulations were separated by autofluorescence-activate d cell sorting using their metabolic responsiveness to 7.5 mM glucose as discriminating parameter. The 7.5 mM glucose responsive and unrespo nsive subpopulations were perifused in parallel in order to compare th eir secretory responses to leucine (10 mM) or to arginine (5 mM); resp onses to glucose were taken as control. Under maximal glucose stimulat ion (20 mM), the responsive subpopulation released two-fold more insul in than the unresponsive one whereas maximal stimulation with leucine (10 mM) elicited similar first and second phase responses in the two s ubpopulations. On the other hand, a maximal arginine stimulus (5 mM) a mplified release only from glucose-activated beta-cells; neither did i t correct the differences in glucose-induced insulin release between b oth subpopulations. These results indicate that rat beta-cells exhibit a heterogeneity in secretory responsiveness to glucose but not to leu cine, a metabolized secretagogue which can induce release in the absen ce of glucose. A heterogeneity is also observed in the cellular respon siveness to arginine, and its secretory effect consists of an amplific ation of glucose-activated cells. (C) 1994 Academic Press, Inc.