Studies on the Action of Na on Insulin Release I: Role of Sodium Ion in the Mechanism of Insulin Release in View of Suppressive Effect of Diphenylhydantoin
1977 Volume 20 Issue 1 Pages 17-22
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1977 Volume 20 Issue 1 Pages 17-22
Sodium ion is considered to be an essential factor for insulin release from the islets of Langerhans in addition to calcium ion. However, inter-relationship between these two ions is still obscure. A commonly used anticonvulsant, diphenylhydantoin (DPH) has been reported to inhibit insulin release in vivo and in vitro, but its precise mechanism has not been clarified. Recently, DPH was shown to reduce Ca uptake in addition to sodium uptake in nerve cells. This paper presents the evidences that alterations of sodium and calcium flux are involved in inhibition of insulin release by DPH using in vitro perifusion system of rat isolated islets of Langerhans.
Results are as follows:
1) DPH (1μg-25μg/rni) inhibits insulin release induced by glucose (16.7mM) dose-dependently.
2) The inhibition by DPH is reversible and the rebound occurs. after withdrawal of DPH.
3) The inhibition of insulin release by DPH is reversed by suppression of Na efflux with ouabain and acceleration of Na influx with gramicidin. These findings suggest that DPH inhibits insulin release by suppression of Na influx as well as acceleration of Na efflux by activation of Na+-K+ ATP-ase.
4) The inhibition of insulin release by DPH (5μg/ ml) is reversed significantly by increased Ca influx with high calcium (11.8 mEq/L) or A 23187 (10-5M).
The above data suggest that inhibition of Na net uptake by DPH suppresses Ca influx, and decreased cytosolic calcium concentration thereby produced inhibits insulin release.
