Phenytoin inhibition of insulin release. Studies on the involvement of Ca2+ fluxes in rat pancreatic islets

The presence of different types [long lasting (L) and transient (T)] of active voltage-operated Ca2+ channels in islet cells was investigated by comparing the effects of Cd2+, Ni2+, and 1,4-dihydropyridines on 45Ca uptake, 45Ca efflux, and insulin release in intact rat pancreatic islets. In several other excitable cells the L-channel has been shown to be modulated by 1,4-dihydropyridines and Cd2+, whereas the T-channel was reported to be sensitive to Ni2+. Nifedipine and Cd2+ inhibited whereas BAY K 8644 enhanced the glucose (11.1, 22.2 mM)-stimulated short-term 45Ca uptake, 45Ca efflux, and insulin release. In contrast, the stimulatory effects of glucose (11.1, 22.2 mM) on 45Ca uptake, 45Ca efflux, and insulin release were unaffected by Ni2+. These findings confirm that glucose provokes Ca2+ entry mainly by activating voltage-sensitive Ca2+ channels of the L-type and suggest that the B-cell plasma membrane is not equipped with active T-type Ca2+ channels.

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Insulin release and arachidonic acid metabolism in neonatal rat pancreatic islets. (2)

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)62400-5 ◽

1984 ◽

Vol 36 ◽

pp. 96

Author(s):

Naoko Tanaka ◽

Shohei Nagawa ◽

Keiko Murakoso ◽

Kunio Haito ◽

Shizuo Shimizu ◽

...

Keyword(s):

Arachidonic Acid ◽

Pancreatic Islets ◽

Insulin Release ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Neonatal Rat ◽

Rat Pancreatic Islets

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Mechanisms of synergism between glucose and cAMP on stimulation of insulin release

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1984.247.6.e701 ◽

1984 ◽

Vol 247 (6) ◽

pp. E701-E708 ◽

Cited By ~ 1

Author(s):

W. Phang ◽

L. Domboski ◽

Y. Krausz ◽

G. W. Sharp

Keyword(s):

Pancreatic Islets ◽

Insulin Release ◽

Ringer Solution ◽

Intracellular Camp ◽

Cyclic Monophosphate ◽

Rat Pancreatic Islets ◽

Individual Effects ◽

The Individual ◽

Isolated Rat ◽

Stimulation Of

The mechanism of synergism between glucose and adenosine 3',5'-cyclic monophosphate (cAMP) on insulin release has been studied. Synergism may result from 1) inhibition of Na+-Ca2+ exchange by glucose and 2) a cAMP-induced sensitization of the release machinery to Ca2+. To distinguish between these two possibilities, isolated rat pancreatic islets were perifused with agents that raise intracellular levels of cAMP [3-isobutyl-1-methylxanthine (IBMX) and forskolin] and others that increase intracellular concentrations of Ca2+ either by blocking Na2+-Ca2+ exchange (ouabain and choline-Ringer solution) or by causing increased Ca2+ influx (KCl, carbachol, and 10 mM Ca2+). The results indicate that both the combination of cAMP and increased Ca2+ influx or blocked Na2-Ca2+ exchange and increased Ca2+ influx potentiated insulin release. When the relative potentiating abilities of cAMP and blocked Na2+-Ca2+ exchange were compared by determining the individual effects of IBMX and 1 mM ouabain (a concentration that causes similar inhibition of 45C2+ efflux as 16.7 mM glucose) in the presence of carbachol, cAMP was only 1.4 times more potent as a potentiating agent than blocked Na+-Ca2+ exchange. The greatest potentiation of insulin release was observed when Na+-Ca2+ exchange was blocked in the presence of increased levels of intracellular cAMP.

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