Regulation by glucose and cyclic nucleotides of the glucagon and insulin release induced by amino acids.

The glucagon and insulin release induced by amino acids was studied in the presence of glucose, dibutyryl cyclic AMP (dbcAMP) or theophylline on the splenic part of the pancreas of new born rats (48 to 64 hours). The results were compared to the literature data. Arginine or a mixture of the three amino acids (A.A.), arginine, lysine or alanine, stimulate glucagon secretion at 1.6 mM glucose. This stimulation is suppressed by 16.7 mM glucose. On the other hand, 16.7 mM glucose potentiates the effect of arginine or of the 3 A.A. on insulin release. At 1.6 mM glucose, theophylline potentiates the effect of 3 A.A. (10 mM each) on glucagon and insulin release : this effect reaches a maximum at 5 mM of theophylline; dbcAMP also potentiates the effect of 3 A.A. on glucagon and insulin release, and the effect of arginine, alanine or lysine on glucagon release. On the beta cell, the lack of potentiation observed between dbcAMP and arginine, lysine or alanine indicates that these A.A. interact positively when mixed together. In the presence of arginine or of the three A.A., the percentage stimulation of glucagon and insulin release depends on the dbcAMP dose and does not vary with the glucose concentration. The increase of glucagon and insulin release observed when the NaCl concentration in the incubation medium decreases cannot account for our results. Cyclic GMP (4 mM) does not modify the glucagon or insulin secretion induced by different concentrations of glucose or by the mixture of A.A. (10 mM each). The stimulating effect of acetylcholine on insulin release would not be related to the cyclic GMP molecule. In conclusion, instead of modifying the specificity of substrate, theophylline or dbcAMP accentuate it: glucose stimulates specifically the beta cell whereas 3 A.A. are more effective on the alpha2 cell than the beta cell. Cyclic AMP suppresses the glucose effect on glucagon release induced by the amino acids. Because of its interaction with glucose and amino acids, cyclic AMP seems to be a very important element in the regulation of the release of these pancreatic hormones.