Amino Acid Stimulation of Glucagon Secretion by Perifused Islets of High-protein-fed Rats

Abstract

Feeding of a high-protein, carbohydrate-free (HP) diet to rats results in elevated plasma glucagon and increased glucagon secretion by isolated islets of Langerhans. Since amino acids liberated during protein digestion may cause increased pancreatic glucagon release, the effects of 21 amino acids on glucagon secretion by perifused islets of HP-fed and control rats were examined. Arginine caused a marked rise of glucagon secretion, which consisted of an initial burst followed by a sustained phase of elevated hormone release. Total glucagon secretion by HP islets in response to arginine was 69.8 ± 5.3 pg./islet/30 minutes and by control islets was 30.0 ± 2.6, P = <0.001. Perifused islets responded physiologically to suppression as well as stimulation, since the arginine effect was abolished by raising the medium glucose level to 16.7 mM or by addition of small amounts of somatostatin (10 ng./ml). Of the 10 essential amino acids, only arginine had a major effect on hormone release by the alpha cell. Glutamine and α-aminobutyrate caused increases of glucagon secretion that were similar in pattern and magnitude to that induced by arginine. Total glucagon secretion by HP islets in response to glutamine was 65.6 ±4.6 pg./islet/30 minutes and by control islets was 39.1 ±8.1. Glucagon release by HP islets in response to α-aminobutyrate was 63.4 ± 4.6 pg./islet/30 minutes. Ornithine caused a sharp rise of glucagon release that was not sustained. Total hormone secretion induced by ornithine amounted to 27.3 ±6.9 pg./islet/30 minutes. None of the other nonessential amino acids, including alanine, had a major effect on pancreatic alpha cell function.