Leucine and arginine are well-known stimulators of insulin release, but they exert different actions on insulin biosynthesis in short-term incubations of isolated islets. In order to study their long-term effects on the B-cell, isolated rat islets were cultivated for 40 h in medium containing 0·5 or 3 mg glucose/ml supplemented with l-leucine (10 mmol/l) or l-arginine (10 mmol/l). After the culture the islets were incubated for 3 h with 2 mg glucose/ml without addition of the respective amino acid. Insulin biosynthesis was estimated from incorporation of [3H]phenylalanine or [3H]leucine into the (pro)insulin fraction of the islet proteins during this incubation.
At the low concentration of glucose, the leucine-cultivated islets released much more insulin than the control islets during culture as well as during subsequent incubation. At both glucose concentrations cultivation together with this amino acid resulted in an enhanced insulin biosynthesis.
The insulin-releasing effect of arginine with 0·5 mg glucose/ml was not as marked as that observed with an equimolar concentration of leucine. Islets cultivated with arginine showed no response to glucose during the incubation after culture. Hormone synthesis was found to be inhibited. Shortening of culture time to 20 h, followed by an additional 4 h of cultivation without arginine did not result in an improvement of B-cell function after culture.
It is concluded that leucine, in contrast with arginine, supports B-cell function, especially insulin biosynthesis, during long-term culture of islets. Stimulation of release of insulin with a concomitant inhibition of insulin biosynthesis caused by arginine during culture did not lead to a compensatory increase in hormone synthesis after culture.
Long-term effects of exposure of pancreatic islets to nicotinamide in vitro on DNA synthesis, metabolism and B-cell function