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

Knudsen, P. ; Kofod, H. ; Lernmark, A. LU orcid and Hedeskov, C. J. (1983) In American Journal of Physiology - Endocrinology and Metabolism 245(4). p.338-346
Abstract

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... (More)

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.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
in
American Journal of Physiology - Endocrinology and Metabolism
volume
245
issue
4
pages
338 - 346
publisher
American Physiological Society
external identifiers
  • pmid:6194691
  • scopus:0020840915
ISSN
0193-1849
language
English
LU publication?
no
id
a20d4ef6-35df-48f8-a134-86ac15e88438
date added to LUP
2019-09-16 12:44:45
date last changed
2025-10-14 13:14:15
@article{a20d4ef6-35df-48f8-a134-86ac15e88438,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Knudsen, P. and Kofod, H. and Lernmark, A. and Hedeskov, C. J.}},
  issn         = {{0193-1849}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{338--346}},
  publisher    = {{American Physiological Society}},
  series       = {{American Journal of Physiology - Endocrinology and Metabolism}},
  title        = {{L-Leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase}},
  volume       = {{245}},
  year         = {{1983}},
}