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 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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology (Consolidated) |
| Volume | 245 |
| Issue number | 4 |
| Pages (from-to) | E338-46 |
| ISSN | 0002-9513 |
| Publication status | Published - Oct 1983 |
Keywords
- 1-Methyl-3-isobutylxanthine
- Animals
- Cell Line
- Glucagon
- Glucose
- Glutamate Dehydrogenase
- Glutamine
- Insulin
- Insulinoma
- Islets of Langerhans
- Kinetics
- Leucine
- Male
- Mice
- Mice, Inbred Strains
- Norepinephrine
- Pancreatic Neoplasms
- Rats