Akt Signals Upstream of L-Type Calcium Channels to Optimize Insulin Secretion

作者：Cui, Xiuli; Yang, Guang; Pan, Minglin; Zhang, Xiao-Nan; Yang, Shao-Nian^*

来源：Pancreas, 2012, 41(1): 15-21.

DOI：10.1097/MPA.0b013e31822363a9

• Akt inhibitor
• calcium ionophore
• insulin release
• pancreatic beta cell
• protein kinase B
• voltage-gated calcium channel

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 beta 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 Ca(2+) 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.

• 出版日期2012-1
• 单位吉林大学; 天津医科大学