Valinomycin inhibition of insulin release and alteration of the electrical properties of pancreatic B cells

Henquin, J.C.; Meissner, H.P.

Biochimica et Biophysica Acta 543(4): 455-464

1978


ISSN/ISBN: 0006-3002
PMID: 363170
DOI: 10.1016/0304-4165(78)90300-8
Accession: 068527050

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Abstract
The effects of valinomycin on insulin release and Rb efflux from perifused isolated rat islets were investigated and correlated with its effects on the electrical properties of mouse .beta. cells studied with microelectrode techniques. Valinomycin produced a (1.10-9-1.10-6 M) dose- and time-dependent inhibition of (10-15 mM) glucose-stimulated insulin release but did not affect basal secretion. This inhibitory effect rapidly followed addition of the ionophore and equally affected the 2 phases of glucose-stimulated secretion. It was not reversible by simple washing of the islets, but could be reversed transiently by tetraethylammonium or high extracellular K+ levels. At low or high glucose, valinomycin rapidly augmented the rate of 86Rb+ efflux from preloaded islets. Amplitude and rapidity of this effect were dose-dependent and it was antagonized by tetraethylammonium. Glucose metabolism by islet cells was reduced only slightly (15%) by 1.10-7 M valinomycin. During the first 6-8 min of valinomycin addition, the membrane potential of .beta. cells augmented slowly but the typical bursts of spikes disappeared rapidly. Later on, B cells hyperpolarized more quickly to a stable value of approximately -70 mV. Increasing extracellular K+ immediately depolarized .beta. cells, and the linear relationship found between the logarithm of K+ concentration and the membrane potential was characterized by a slope of 58 mV for a 10-fold increase in extracellular K+. Valinomycin probably interferes with the insulin releasing effect of glucose by increasing the K permeability of the .beta. cell membrane.