Possible participation of an islet B-cell calcium-sensing receptor in insulin release.
The calcium-sensing receptor gene was recently shown to be expressed in rat pancreatic islets and purified islet B-cells. In this study, we investigated the possible role of this receptor in the regulation of insulin release from isolated rat pancreatic islets. Poly-L-arginine (0.2-0.3 microM) and poly-L-lysine (0.03-0.1 microM) increased insulin output evoked by D-glucose (8.3 mM). This positive effect faded out at higher concentrations of the basic peptides. Likewise, the release of insulin evoked by 8.3 mM D-glucose was significantly lower at high (1.0 mM) than low (0.05-0.1 mM) concentrations of neomycin. The insulinotropic action of Ba2+ in Ca2+-deprived islets was potentiated in rats pretreated with pertussis toxin. However, Gd3+ inhibited insulin release evoked by D-glucose in islets prepared from normal rats or animals pretreated with pertussis toxin and incubated in the absence or presence of either theophylline or forskolin. Gd3+ (0.3 mM) failed to affect effluent radioactivity from islets prelabeled with myo-[2-3H]inositol and cyclic AMP net production in islets incubated in the absence or presence of forskolin. Gd3+ decreased, however, 45Ca efflux from prelabeled islets perifused in the absence or presence of extracellular Ca2+. It is speculated that a negative insulinotropic action mediated by the calcium-sensing receptor, and possibly attributable to a fall in cytosolic Ca2+ concentration, may prevent excessive insulin secretion in pathological situations of hypercalcemia.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium. malaisse@med.ulb.ac.be
Louchami
K
K
Laghmich
A
A
Ladrière
L
L
Morales
M
M
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Rasschaert
J
J
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D007700:Kinetics; D009355:Neomycin / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D011107:Polylysine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D010455:Peptides; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; C473605:extracellular calcium cation-sensing receptor, rat; D001464:Barium; D011107:Polylysine; C015462:polyarginine; D007294:Inositol; D005682:Gadolinium; D000242:Cyclic AMP; D037342:Pertussis Toxin; D009355:Neomycin; D005947:Glucose; D002118:Calcium