L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase.
Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthesized. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas the Km for glucose-stimulated insulin release was unaffected by 1 mmol/liter L-leucine OMe, the maximal release of D-glucose was increased by the amino acid derivative that appeared more effective than L-leucine. L-Leucine OMe was also a potent stimulus of insulin release from the perfused mouse pancreas. In the presence of 10 mmol/liter L-glutamine, 1 mmol/liter L-leucine OMe induced a 50- to 75-fold increase in insulin release. A similar stimulatory effect was also observed in column-perifused RIN 5F cells, a cloned rat islet tumor cell line. A twofold increase in islet glutamate dehydrogenase activity was induced by 5 mmol/liter L-leucine OMe, a larger effect than that of L-leucine (P less than 0.02), whereas L-arginine OMe had a small inhibitory effect. We conclude that L-leucine OMe is a potent stimulus of insulin secretion and that its effect on the beta-cells may be exerted by activating islet glutamate dehydrogenase.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism; D051381:Rats
D007328:Insulin; D005973:Glutamine; C030365:leucine methyl ester; D005934:Glucagon; D005969:Glutamate Dehydrogenase; D007930:Leucine; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine