28Mg2 + uptake by rat islets was measured during incubation with various stimulators or inhibitors of insulin releasc. D-Glucose induced a dose-dependent increase in 28Mg2f uptake after 10 min or 120 min. The threshold concentration was around 6 mM and the maximum effect was observed with 15 -20 mM glucose. After 120 min ptake was also stimulated by the metabolized sugars mannose, N-acetylglucosamine or glyceraldehyde, was unaffected by the non-metabolized or poorly metabolized L-glucose, galactose, 3-O-methylglucose, 2-deoxyglucose, fructose or mannoheptulose and was inhibited by glucosamine. The effect of glucose was markedly impaired by mannoheptulose, glucosamine, aminooxyacetate and NHaC1, but was only partially decreased by D600 or diazoxide, which were ineffective in a glucose-free medium. Tolbutamide or KCl slightly increased 28Mg2+ uptake. Alanine, leucine alone or with glutamine, and ketoisocaproate also stimulated "Mg2+ uptake, whereas arginine and lysine decreased it. These changes in "Mg'+ uptake, brought about by various modifiers of the B-cell function, are thus similar but not identical to the changes in Ca2+ uptake, and are not the consequence of insulin release. The stimulatory effect of glucose requires glucose metabolism by islet cells, but is only partially due to depolarization of the B-cell membrane.Intracellular Mg2+ plays an essential role in the control of cellular activity by regulating the activity of numerous enzyme systems. In comparison to calcium, however, only few studies have focused on the cellular metabolism of Mg". Its transport systems have been characterized in some tissues (for review, see [l]) but the possible regulation of this transport by physiological or pharmacological agents has been investigated only rarely.It has been reported that epinephrine increases '*Mg2' uptake and total Mg" content in rat adipocytes [2], but the mechanism of this stimulation is controverted. It has been ascribed to activation of both CL and /?-adrenergic (a > p) receptors [3] or of 8-adrenergic receptors only [4]. On the other hand, /I-adrenergic agonists were found to inhibit 28Mg2+ uptake in S49 lymphoma cells and GM86 erythroleukemia cells [5], and to block an inward Mg" current in myocardial fibres [6]. Prostaglandin El also decreased "Mgz+ uptake by S49 cells, but neither this inhibition nor that produced by ,!3-adrenergic agents was mediated by cyclic AMP [7]. In vivo experiments in rabbits have shown that glucose and insulin synergistically act to increase "Mg2+ uptake and Mg2+ content in various tissues, in particular in heart and skeletal muscle [8]. In vitro insulin was found to stimulate Mg2 + accumulation in uterine smooth muscle [9] and in chicken embryo fibroblasts [lo] by still unidentified mechanisms. "Mg" transport into rat liver slices was not affected by glucose depletion [l We have previously reported [I 31 that glucose, the major regulator of the functioning of the endocrine pancreas, markedlpmodifies 28Mg2+ fluxes in rat islet cells. To gain a better insight into the...