1. Academic Validation
  2. VPAC2 receptor mediates VIP-potentiated insulin secretion via ion channels in rat pancreatic β cells

VPAC2 receptor mediates VIP-potentiated insulin secretion via ion channels in rat pancreatic β cells

  • Exp Cell Res. 2023 Jan 12;113471. doi: 10.1016/j.yexcr.2023.113471.
Xin Zhao 1 Lijiao Deng 1 Lele Ren 1 Huanhuan Yang 1 Bin Wang 1 Xiaochan Zhu 1 Xiaoli Zhang 1 Chao Guo 1 Yi Zhang 2 Yunfeng Liu 3
Affiliations

Affiliations

  • 1 Department of Pharmacology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 2 Department of Pharmacology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: [email protected].
  • 3 Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: [email protected].
Abstract

Vasoactive intestinal peptide (VIP), a small neuropeptide composing of 28 Amino acids, functions as a neuromodulator with insulinotropic effect on pancreatic β cells, in which it is of vital importance in regulating the levels of blood glucose. VIP potently agonizes VPAC2 receptor (VPAC2-R). Agonists of VPAC2-R stimulate glucose-dependent Insulin secretion. The purpose of this study was to further investigate the possible ion channel mechanisms in VPAC2-R-mediated VIP-potentiated Insulin secretion. The results of Insulin secretion experiments showed that VIP augmented Insulin secretion in a glucose-dependent manner. The insulinotropic effect was mediated by VPAC2-R rather than VPAC1 receptor (VPAC1-R), through the adenylyl cyclase (AC)/protein kinase A (PKA) signalling pathway. The calcium imaging analysis demonstrated that VIP increased intracellular Ca2+ concentration ([Ca2+]i). In addition, in the whole-cell voltage-clamp mode, we found that VIP blocked the voltage-dependent potassium (Kv) channel currents, while this effect was reversed by inhibiting the VPAC2-R, AC or PKA respectively. Taken together, these findings suggest that VIP stimulates Insulin secretion by inhibiting the Kv channels, activating the Ca2+ channels, and increasing [Ca2+]i through the VPAC2-R and AC/PKA signalling pathway. These findings provide theoretical basis for the research of VPAC2-R as a novel therapeutic target.

Keywords

Insulin secretion; Ion channels; VPAC2 receptor; Vasoactive intestinal peptide; β cell.

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