Role of Extracellular Magnesium in Insulin Secretion from Rat Insulinoma Cells

Magnesium (Mg²⁺) is an abundant intracellular cation that participates in the regulation of the intracellular concentration of ATP. In this study, we examined the relationship between insulin secretion and intracellular free Mg²⁺ ([Mg²⁺]ⁱ) in a rat-insulinoma cell line (RIN m5F), using a fluorescent dye (Mag-fura-2). KCI, forskolin, and D-glyceraldehyde increased [Mg²⁺]ⁱ and insulin secretion from RIN m5F cells in a dose-dependent fashion. Verapamil, a voltage-dependent Ca²⁺ channel blocker, inhibited the increase of [Mg²⁺]ⁱ that was evoked by KCI, forskolin, and D-glyceraldehyde. In a Mg²⁺-free buffer, these agents failed to cause an elevation in [Mg²⁺]ⁱ; however, the insulin response to KCI and forskolin was enhanced, compared with that in the presence of Mg²⁺ (1.25 mM). Our findings suggest that [Mg²⁺]ⁱ is dependent upon extracellular Mg²⁺, and the influx through the voltage-dependent Ca²⁺ channel. Mg²⁺ may competitively inhibit the voltage-dependent Ca²⁺ channel, which is known to play a role in insulin secretion. An absence of Mg²⁺ in the extracellular space may result in enhanced insulin secretion. [Mg²⁺]ⁱ may play a role in insulin secretion from RIN m5F cells.