GIP/GIPR经Akt-TCF4-GIPR正反馈增强GIP效应

doi:10.11843/j.issn.0366-6964.2020.09.009

Abstract

Abstract: The purpose of this study was to screen the regulatory factors that regulate the expression of GIPR from the downstream Akt and PKA signal pathways of GIP/GIPR, and to analyze the regulatory mechanism of GIPR expression. In this study, mouse insulinoma cell line Min6 was used as experimental material, under the condition of blocking Akt and PKA signal pathways, transcription factor T cytokine 4 (TCF4) related to GIPR expression was screened by Western blot, the effect of TCF4 on the regulation of GIPR expression was determined by double luciferase reporter system, and the relationship between TCF4 and GIPR was further verified by knockout or overexpression of TCF4. The proliferation-promoting effect mediated by TCF4 was detected by CCK8 method, and the ability of insulin secretion was detected by ELISA. The results showed that GIP could activate Akt phosphorylation and promote the expression of GIPR; when GIP was activated and Akt and PKA signal pathways were blocked, the expression trend of GIPR protein was consistent with that of TCF4; TCF4 could bind to the core promoter of GIPR and regulate its expression; when TCF4 was overexpressed, the mRNA and protein expression of GIPR were up-regulated, and β-cell proliferation and insulin secretion were promoted. Interfering with TCF4 significantly decreased the mRNA and protein expression of GIPR under the action of GIP, and inhibited the proliferation of β-cell. In conclusion, after GIP is combined with GIPR, TCF4 is upregulated through Akt signal pathway to enhance the expression of GIPR, which forms a positive feedback to enhance GIP signal, and enhance the function of β-cell proliferation and insulin secretion to maintain blood glucose homeostasis. Therefore, when insulin resistance blocks Akt and upstream signal pathway, the enhancement of GIPR expression by transcription factor TCF4 can be used as a target to improve islet β-cell dysfunction.

Key words: glucose dependent insulinotropic polypeptide receptor, T cell factor 4, Akt signal pathway, Min6 cell

CLC Number:

S852.2

YE Huaqiong, AN Cuiping, ZHANG Kaiyi, XIE Ning, BI Yanzhen, YANG Shulin, LI Shenghe. GIP/GIPR Enhanced GIP Effect by Positive Feedback of Akt-TCF4-GIPR[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(9): 2120-2129.

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GIP/GIPR Enhanced GIP Effect by Positive Feedback of Akt-TCF4-GIPR

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