L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase
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L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase. / Knudsen, P; Kofod, Hans; Lernmark, A; Hedeskov, C J.
In: American Journal of Physiology (Consolidated), Vol. 245, No. 4, 10.1983, p. E338-46.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase
AU - Knudsen, P
AU - Kofod, Hans
AU - Lernmark, A
AU - Hedeskov, C J
PY - 1983/10
Y1 - 1983/10
N2 - 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.
AB - 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.
KW - 1-Methyl-3-isobutylxanthine
KW - Animals
KW - Cell Line
KW - Glucagon
KW - Glucose
KW - Glutamate Dehydrogenase
KW - Glutamine
KW - Insulin
KW - Insulinoma
KW - Islets of Langerhans
KW - Kinetics
KW - Leucine
KW - Male
KW - Mice
KW - Mice, Inbred Strains
KW - Norepinephrine
KW - Pancreatic Neoplasms
KW - Rats
M3 - Journal article
C2 - 6194691
VL - 245
SP - E338-46
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 4
ER -
ID: 45575352