Stimulus-secretion coupling of arginine-induced insulin release: comparison between the cationic amino acid and its methyl ester.
The role currently ascribed to the accumulation of L-arginine in the pancreatic islet B-cell as a determinant of its insulinotropic action was reevaluated by comparing the uptake and the metabolic, ionic, electric, and secretory effects of the cationic amino acid with those of its more positively charged methyl ester in rat pancreatic islets. The response to L-arginine methyl ester differed from that evoked by the unesterified amino acid by a lower uptake and oxidation, lack of inhibitory action on D-glucose metabolism, more severe inhibition of the catabolism of endogenous L-glutamine, inhibition of 45Ca net uptake, decrease in both 86Rb outflow from prelabeled islets perifused at normal extracellular Ca2+ concentration and 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca2+, and delayed and lesser insulinotropic action. These findings reinforce the view that the carrier-mediated entry of L-arginine into the islet B-cells, with resulting depolarization of the plasma membrane, represents the essential mechanism for stimulation of insulin release by this cationic amino acid.
Sener
A
A
Laboratory, of Experimental Medicine, Brussels Free University, Belgium.
Best
L C
LC
Yates
A P
AP
Kadiata
M M
MM
Olivares
E
E
Louchami
K
K
Jijakli
H
H
Ladrière
L
L
Malaisse
W J
WJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002250:Carbon Radioisotopes; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000378:metabolism
D002132:Calcium Radioisotopes; D002250:Carbon Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes; D005973:Glutamine; C026512:arginine methyl ester; D009569:Nitric Oxide; D001120:Arginine; D005947:Glucose; D002118:Calcium