The partial protective effect of branched chain amino acids against streptozotocin-induced cytotoxicity to mouse pancreatic islets in vitro.

Recent experiments suggested that injections of branched chain amino acids (BCAA) immediately followed by streptozotocin (SZ), induced a partial protection against the diabetogenic action of SZ in vivo. In the present investigation, isolated mouse pancreatic islets were exposed in vitro to SZ (2.2-4.4 mM), with or without preincubation in a mixture of BCAA (15 mM leucine, 15 mM isoleucine and 15 mM valine). In order to evaluate the toxic action of SZ on the beta-cell, the islets were studies after culture for 3 days following SZ exposure. In control islets which had not been pretreated with BCAA, 4.4 mM SZ induced a 47% diminution in the islet number, while only 20% were lost after pretreatment with BCAA. There was also a greater total islet DNA content recovered in the islets pretreated with BCAA before SZ exposure. The BCAA islets furthermore maintained a slightly higher insulin release to the culture medium, insulin content and insulin response to an acute glucose stimulus. Preincubation with each of the amino acids alone did not protect against the SZ action. The present data are consistent with previous in vivo findings and suggest that a direct BCAA-induced decrease in the beta-cell sensitivity to SZ can explain the partial protective effect of these amino acids against the diabetogenic action of SZ.