Volume 21 Issue 3
Mar.  2023
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ZHUANG Langen, JIN Guoxi, YANG Qingqing, HU Xiaolei, PEI Xiaoyan. The influence of liraglutide on insulin secretion function of E23K mutation of Kir6.2 gene in β cells[J]. Chinese Journal of General Practice, 2023, 21(3): 385-388. doi: 10.16766/j.cnki.issn.1674-4152.002889
Citation: ZHUANG Langen, JIN Guoxi, YANG Qingqing, HU Xiaolei, PEI Xiaoyan. The influence of liraglutide on insulin secretion function of E23K mutation of Kir6.2 gene in β cells[J]. Chinese Journal of General Practice, 2023, 21(3): 385-388. doi: 10.16766/j.cnki.issn.1674-4152.002889

The influence of liraglutide on insulin secretion function of E23K mutation of Kir6.2 gene in β cells

doi: 10.16766/j.cnki.issn.1674-4152.002889
Funds:

 BYTM2019032

 1908085QH319

  • Received Date: 2022-01-11
    Available Online: 2023-04-19
  •   Objective  Polymorphism of Kir6.2 is associated with diabetes and insulin resistance. This study aims to explore whether liraglutide can improve the insulin secretion function and mechanism of the E23K mutation of Kir6.2 gene of β cell of islet under a high glucose condition.  Methods  Taking NIT-1 cells as the object, Kir6.2 gene-overexpressed wild-type and E23K mutant NIT-1 cells were constructed, and liraglutide was adopted to intervene in a high-glucose environment for 24 hours. Flow cytometry was used to detect the NIT-1 cell apoptosis rate, the cell membrane potential and the calcium ion concentration. Western blotting and immunofluorescence assay were conducted to detect insulin contents in cells. ELISA was utilized to detect insulin contents in nutrient fluid, based on which insulin secretion was indirectly studied.  Results  NIT-1 cells had an optimal high glucose culture concentration of 60 mmol/L, with the highest amount of insulin synthesis, whereas 10 mmol/L was selected for liraglutide in vitro. The insulin secretion of Kir6.2 gene-overexpressed wild-type NIT-1 cells was higher than that of Kir6.2 gene E23K mutant NIT-1 cells. The Kir6.2 gene-overexpressed wild-type NIT-1 cells presented less membrane potential and higher Ca2+ concentration in cells in a high-glucose environment, while Kir6.2 gene E23 mutant NIT-1 cells made no significant changes compared with those cultured under high glucose concentration. Liraglutide could effectively reduce apoptosis of wild-type and mutant NIT-1 cells, decrease membrane potential, increase Ca2+ concentration in the cells, and promote insulin secretion in a high-glucose environment. In addition, liraglutide was of greater significance to the survival of mutant NIT-1 cells.  Conclusion  In a high-glucose environment, liraglutide can improve the insulin secretion function of polymorphic of E23K site Kir6.2 gene islet β cell. This study provides basic evidence for the clinical application of liraglutide.

     

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