The interaction between manganese and calcium fluxes in pancreatic β-cells

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Abstract
Electrothermal atomic-absorption spectroscopy was employed for measuring Mn in .beta.-cell-rich pancreatic islets isolated from ob/ob mice. The efflux from preloaded islets was estimated from the amounts remaining after 30 min of subsequent test incubations in the absence of Mn2+. An increase in the extracellular Mg2+ concentration promoted the Mn2+ efflux and removal of Na+ from a Ca2+-deficient medium had the opposite effect. Addition of 25 mM-K+ failed to affect Mn2+ outflow as did 3-isobutyl-1-methylxanthine and dibutyryl cAMP. Whereas tolbutamide caused retention of Mn, the ionophore Br-X537A prmoted an efflux. D-Glucose was equally potent in retaining the islet Mn when the external Ca2+ concentration ranged from 15 .mu.M to 6.30 mM. Subcellular-fractionation experiments indicated a glucose-stimulated incorporation of Mn into all fractions except the microsomes. The effect was most pronounced in the mitochondrial fraction, being as high as 164%. The glucose-induced uptake of intracellular 45Ca was abolished in the presence of 0.25 mM-Mn2+. When added to medium containing 2.5 mM-Mn2+, glucose even tended to decrease 45Ca2+ uptake. The inhibitory effect of Mn2+ was apparent also from a diminished uptake of 45Ca into all subcellular fractions. The efflux of 45Ca2+ was markedly influenced by Mn2+ as manifested in a prominent stimulation followed by inhibition. In addition to demonstrating marked interactions between fluxes of Mn2+ and Ca2+, these studies support the view that the glucose inhibition of the efflux of bivalent cations from pancreatic .beta.-cells is accounted for by their accumulation in the mitochondria.