Stimulus-secretion coupling of arginine-induced insulin release. Functional response of islets to L-arginine and L-ornithine.
L-Arginine and L-ornithine stimulate insulin release from pancreatic islets exposed to D-glucose. This coincides with an increased outflow of 86Rb and 45Ca from prelabelled islets and an increased net uptake of 45Ca by the islets. In the presence of D-glucose, L-lysine stimulates insulin secretion to the same extent as L-arginine or L-ornithine, but the hormonal release is not further enhanced by combinations of these cationic amino acids. L-Arginine or L-ornithine failed to enhance insulin release evoked by either L-leucine or 2-ketoisocaproate. The inhibitor of ornithine decarboxylase D,L-alpha-difluoromethyl ornithine failed to affect the metabolism and insulinotropic action of D-glucose in pancreatic islets, and only caused a partial inhibition of the secretory response to either L-arginine or L-ornithine. The latter amino acids inhibited modestly but significantly D-glucose utilization and oxidation by pancreatic islets. These and complementary findings suggest that the secretory response to L-arginine and L-ornithine is not attributable to any major change in the overall oxidative catabolism of nutrients, but involves mainly a biophysical component, such as the depolarization of the plasma membrane by these cationic amino acids.
Blachier
F
F
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Leclercq-Meyer
V
V
Marchand
J
J
Woussen-Colle
M C
MC
Mathias
P C
PC
Sener
A
A
Malaisse
W J
WJ
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D009952:Ornithine / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011073:Polyamines / Q000096:biosynthesis; D051381:Rats
D007328:Insulin; D011073:Polyamines; D007294:Inositol; D001120:Arginine; D009952:Ornithine; D005947:Glucose; D008239:Lysine; D002118:Calcium; D000518:Eflornithine