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Åke Lernmark

Principal investigator

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L-Leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase


  • P. Knudsen
  • H. Kofod
  • A. Lernmark
  • C. J. Hedeskov

Summary, in English

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 synthetised. 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 K(m) 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 < 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 β-cells may be exerted by activating islet glutamate dehydrogenase.

Publishing year





American Journal of Physiology - Endocrinology and Metabolism





Document type

Journal article


American Physiological Society




  • ISSN: 0193-1849