Role of extracellular Na+ on CCK-8-induced insulin secretion.
CCK-8 stimulates insulin secretion by an effect involving phosphoinositide (PI) hydrolysis and release of Ca2+ from intracellular stores. In this study, we examined the dependence of Na+ for the effects of CCK-8. CCK-8 (100 nM) stimulated insulin secretion from isolated rat islets. A first phase, which lasted 10 min, was not affected by removal of external Na+, whereas a second phase was abolished. CCK-8-stimulated 45Ca2+ and 3H efflux in 45Ca(2+)- and myo-[2-3H]-inositol-prelabelled islets were not affected by removal of external Na+. In a second series of experiments, pancreatic rat islet cells were loaded with the Ca2+ fluorophore FURA 2-AM. CCK-8 (100 nM) induced a rapid and transient increase in the cytoplasmic free Ca2+ concentration ([Ca2+]IC), followed by a subsequent reduction of [Ca2+]IC below the prestimulatory levels. The CCK-8-induced increase in [Ca2+]IC was not dependent on extracellular Na+, whereas the decline in [Ca2+]IC after the initial peak was slower in the absence than in the presence of Na+. Thus, the present study shows that both the second phase of CCK-8-stimulated insulin secretion and the CCK-8-stimulated postpeak reduction in [Ca2+]IC are dependent on extracellular Na+.
Department of Pharmacology, Lund University, Sweden.
T
T
Fridolf
S
S
Karlsson
B
B
Ahrén
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D005947:Glucose / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D005456:Fluorescent Dyes; D007328:Insulin; C049925:fura-2-am; D007294:Inositol; D012964:Sodium; D005947:Glucose; D012844:Sincalide; D002118:Calcium; D016257:Fura-2