Objectives: Both the serine/threonine protein kinase Akt and the voltage-gated L-type calcium channel act as important players in glucose-stimulated insulin secretion. Akt recruits the L-type calcium channel to and maintains them in the plasma membrane. This study aimed to characterize the role of L-type calcium channels in mediation of Akt signaling in glucose-stimulated insulin secretion.
Methods: Insulin secretion was evaluated in rat pancreatic islets and INS-1 pancreatic β cells by a standard insulin radioimmunoassay.
Results: Akt inhibition effectively abrogates not only glucose-stimulated but also potassium depolarization-stimulated insulin secretion from rat islets, the latter critically relying on the voltage-gated calcium channel-mediated Ca2+ influx without involvement of glucose metabolism. Likewise, Akt inhibition also reduces both glucose-stimulated and potassium depolarization–stimulated insulin secretion from INS-1 cells. Importantly, pharmacological ablation of L-type calcium channels partially blocks Akt inhibition–induced reduction in glucose-stimulated insulin secretion but completely prevents that in potassium depolarization–evoked insulin release from INS-1 cells. Furthermore, Akt inhibition does not influence calcium ionophore A23187-induced insulin secretion from INS-1 cells, which occurred without involvement of L-type calcium channels.
Conclusions: Akt signals upstream of L-type calcium channels to optimize glucose-stimulated insulin secretion.
Abbreviations: CaV - voltage-gated calcium