Stimulus-secretion coupling of arginine-induced insulin release: comparison with histidine-induced insulin release.
L-Histidine, when tested at a 10-mM concentration, caused a rapid and sustained stimulation of insulin release from rat islets exposed to either D-glucose (7.0 or 8.3 mM) or L-leucine (10.0 mM). The stimulation of insulin release could not be ascribed to an increase in oxygen uptake, to the generation of histamine from L-histidine, or to its participation in a transglutaminase-catalyzed reaction. Like other cationic amino acids, however, L-histidine rapidly accumulated in islet cells, increased 86Rb outflow from prelabeled islets perifused in the presence or absence of extracellular Ca2+, and stimulated the entry of Ca2+ into islet cells. Yet, the amount of exogenous L-histidine present in the islet cells with a positively charged side chain was estimated to be below the threshold value required for stimulation of insulin release by fully ionized cationic amino acids, such as L-arginine. Hence, the present findings argue against the view that the insulinotropic action of cationic amino acids is solely attributable to the accumulation of these positively charged molecules inside the islet B cell with subsequent depolarization of the plasma membrane.
Sener
A
A
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Blachier
F
F
Rasschaert
J
J
Malaisse
W J
WJ
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002412:Cations; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006639:Histidine / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009952:Ornithine / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes
D002412:Cations; D007328:Insulin; D012414:Rubidium Radioisotopes; D006639:Histidine; D004533:Egtazic Acid; D006632:Histamine; D001120:Arginine; D009952:Ornithine; D005947:Glucose; D002118:Calcium