Abstract
A possible interaction between Cd
2+ and Ca
2+ as a component in Cd
2+-induced insulin release was investigated in β cells isolated from obese hyperglycemic mice. The glucose stimulated Cd
2+ uptake was dependent on the concentration of sugar. This uptake was sigmoidal with a
K
m for glucose of about 5 mM and was suppressed by both 50 μM of the voltage-activated Ca
2+ channel blocker D-600 and 12 mM Mg
2+. In the presence of 8 mM glucose 5 μM Cd
2+ evoked a prompt and sustained stimulatory response, corresponding to about 3-fold of the insulin release obtained in the absence of the ion. Whereas 5 μM Cd
2+ was without effect on the glucose-stimulated
45Ca efflux in the presence of extracellular Ca
2+, 40 μM inhibited it. At a concentration of 5 μM, Cd
2+ had no effect on the resting membrane potential or the depolarization evoked by either glucose or K
+. In the absence of extracellular Ca
2+ there was only a modest stimulation of
45Ca efflux by 5 μM Cd
2+. Studies of the ambient free Ca
2+ concentration maintained by permeabilized cells also indicate that 5 μM Cd
2+ do not mobilize intracellularly bound Ca
2+ to any great extent. On the contrary, at this concentration, Cd
2+ even suppressed inositol 1,4,5-trisphosphate (IP
3)-induced Ca
2+ release. The present study suggests that Cd
2+ stimulates insulin release by a direct mechanism which does not involve an increase in cytoplasmic free Ca
2+ concentration.
