Insulin Release from the Isolated Perfused Rat Pancreas Induced by L-Leucine, 2-Aminonorbornane-2-carboxylic Acid and α-Ketoisocaproic Acid

Abstract

Kinetics of insulin release from the isolated perfused rat pancreas were studied in the presence of L-leucine, the leucine-analogue 2-aminonorbornane-2-carboxylic aid (BCH) and the transamination derivative of L-leucine, α-ketoisocaproic acid (KIC). 10 mM KIC stimulated insulin secretion within 30 sec. Even when applied to a pancreas perfused with 40 mM L-leucine plus 5 mM glucose 10 mM KIC caused a significant rise of insulin release within 30 sec, while a significant onset of insulin release in the presence of L-leucine (10 mM) was observed after 60 sec. The non-metabolizable leucine-analogue BCH triggered insulin release after 90 sec in absence and after 60 sec in the presence of 5 mM glucose. 10 mM L-norvaline failed to stimulate insulin release both in the absence and presence of 5 mM glucose. In this study 10 mM KIC was found to be a more effective secretagogue than BCH, while BCH was more effective than 10 mM L-leucine. The non-stimulatory concentration of 5 mM glucose changed the patterns of insulin release as caused by L-leucine and BCH. The rapid onset of insulin release and the different patterns of response support the conclusion that KIC and BCH stimulate insulin release not via L-leucine. 1 Dedicated to Professor Dr. H.A. Kühn on the occasion of his 60th birthday