PKCα promotes insulin secretion via TRPC1 phosphorylation in INS-1E cells

ABSTRACT

Protein kinase C (PKC) is a class of phospholipid-dependent serine/threonine kinases that contribute to cell survival, migration, and invasion. Previous studies demonstrated that PKC participates in insulin secretion. However, the role of PKC in glucose-stimulated insulin secretion (GSIS) remains unclear. Herein, we demonstrated that PKC is an important mediator of insulin secretion and revealed a close relationship between PKC activation and insulin secretion in INS-1E cells. Meanwhile, the presence of PKCα was found to induce TRPC1 phosphorylation in INS-1E cells. TRPC1 phosphorylation levels increased by activating PKCα activity. Inhibition of PKCα activity reduced TRPC1 phosphorylation. Finally, we showed that TRPC1 could reverse the decrease in intracellular Ca²⁺ levels and reduced insulin secretion induced by treatment with PKCα inhibitor under high glucose conditions. In conclusion, our findings indicated that TRPC1 and PKCα are involved in promoting insulin secretion and that PKCα promotes insulin secretion via TRPC1 phosphorylation in INS-1E cells.

Graphical Abstract

The effect of PKCα is on insulin secretion in pancreatic β-cells. High glucose-enhanced PKCα activation in pancreatic β-cells. And PKCα activation promoted TRPC1 phosphorylation. Meanwhile, insulin secretion increased when the level of TRPC1 phosphorylation enhanced.

KEYWORDS:

• Protein kinase C α（PKCα)
• transient receptor potential canonical channel-1 (TRPC1)
• insulin secretion
• calcium(Ca²⁺)

Author Contributions

All authors contributed to this work. Conceptualization: Bingyin Shi. Methodology: Jing Xu, Wei Zhang, and Wei Cui. Validation：Jing Xu, Wei Zhang, Wei Cui, Huifang Wang. Formal Analysis：Bingyin Shi, and Jing Xu. Investigation: Jing Xu, Wei Zhang. Resources: Jing Xu, Wei Zhang, Wei Cui, and Huifang Wang. Data Curation: Bingyin Shi. Writing-Original draft: Jing Xu, and Wei Zhang. Writing-Review and editing: Bingyin Shi; Visualization: Jing Xu, and Wei Zhang. Supervision: Bingyin Shi. Project Administration: Bingyin Shi. Funding acquisition: Jing Xu and Bingyin Shi.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by The First Affiliated Hospital of Xi’an Jiaotong University Foundation  [2017QN-16].