In vitro stimulation of insulin release by non-metabolizable, transport-specific amino acids.

The insulin-releasing ability and uptake characteristics of non-metabolizable, transport-specific amino acids were studied in an in vitro system, using microdissected pancreatic islets with more than 9 ° O//o/~-cells. Among the four stereoisomers of 2-aminobicyclo(2,2,i)heptane-2-carboxylic acid (BCH), only the b(-) form stimulated insulin release. This isomer is known as a specific substrate for transport system L in other cells. I t was rapidly taken up by the islet cells and stimulated insulin release both in the presence and in the absence of glucose. 4-Amino-I-guanylpiperidine-4-carboxylic acid (GPA), a substrate for cationic transport systems, stimulated insulin release in the presence but not in the absence of glucose. In this respect GPA is similar to arginine. Like arginine, GPA also accumulated in the islet cells to yield distribution ratios well above unity. The results are consonant with the previous hypothesis that amino acids stimulate insulin release by binding to specific transport molecules.