Cationic Environment and Dynamics of Insulin Secretion - IV. Effect of Ouabain[*]

Abstract

The modifications of glucose- (300 mg/100 ml) and K⁺- (24 mM) induced immunoreactive insulin (IRI) secretion by ouabain (10^-4 M) have been studied in a dynamic system utilizing the perifusion of isolated rat islets. When the glycoside was added to the medium at the time of glucose stimulation, no significant change was noted in either phase of the release; by contrast, the presence of ouabain for 25 or 55 min before stimulation resulted in a diminution of the late phase of IRI secretion. 10^-4 M ouabain impaired the rapid secretory response of the islets to 24 mM K⁺ in the presence of 50 mg glucose/100 ml and reduced the second phase of release provoked by a combination of 300 mg glucose/ 100 ml and 24 mM K⁺. The marked alteration of the insulinotropic effect of glucose observed when a high K⁺ concentration was present before stimulation by the sugar, was still aggravated by the glycoside.

It is suggested that the effects of ouabain on IRI secretion are mediated by the blockade of the Na⁺ /K⁺ pump. In particular, cellular K⁺ depletion might account for the inhibitory effect of the drug.

Key words

Insulin Secretion - Isolated Islets - Perifusion - Ouabain - Potassium - Glucose

1 This investigation was supported by grant 20029 of the Fonds de la Recherche Scientifique Médicale, Brussels, Belgium.

1 This investigation was supported by grant 20029 of the Fonds de la Recherche Scientifique Médicale, Brussels, Belgium.

2 Aspirant du Fonds National de la Recherche Scientifique, Brussels, Belgium.