The role of calcium in insulin release from the human fetal pancreas.
Previous experiments have established that the human fetal pancreas is relatively unresponsive to glucose as regards insulin release, but will secrete this hormone when exposed to agents which increase levels of cAMP or which activate protein kinase C. The current experiments were designed to establish which role another major stimulus, calcium, had in the release of insulin from this organ. For this purpose, cultured explants of human fetal pancreas were exposed to stimuli either in static or dynamic stimulation. The data show that insulin release is enhanced in the presence of 10 mM Ca2+, as well as the calcium ionophores A23187 and ionomycin, the latter agent being effective only if extracellular Ca2+ was present. A biphasic response was seen for Ca2+ but only a second phase response for A23187. Voltage-dependent calcium channels were shown to be present by the ability of the calcium channel blocker, verapamil, to inhibit insulin release caused by an agent that depolarizes membranes, potassium. The essential role of extracellular calcium in the insulinogenic effect of agents which increase cAMP levels--theophylline--and which activate protein kinase C--12-O-tetradecanoylphorbol-13-acetate--was demonstrated by showing (a) partial inhibition of insulin secretion by calcium channel blockers, (b) no enhancement of insulin release in the absence of extracellular calcium and (c) greater enhancement of insulin release in the presence of the calcium channel activator BAY-K-8644, which caused no stimulation by itself. These data put into better perspective our understanding of the mechanisms involved in insulin release from the human fetal pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
Tuch
B E
BE
Department of Medicine, University of Sydney, Australia.
Osgerby
K J
KJ
Turtle
J R
JR
D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007476:Ionophores / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D007476:Ionophores; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium