open access

Vol 75, No 1 (2024)
Original paper
Submitted: 2023-05-11
Accepted: 2023-07-31
Published online: 2023-11-29
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sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes

Xin Qu12, Xiao-yan Li1, Yan Feng3, Xiaoli Wang1, Lei Li1, Yu-ping Wang1, Yong-li Chu12
·
Pubmed: 38497391
·
Endokrynol Pol 2024;75(1):61-70.
Affiliations
  1. Department of Obstetrics and Gynaecology, Yantai Yuhuangding Hospital, Yantai, China
  2. Cheeloo College of Medicine, Shandong University, Jinan, China
  3. Department of Clinical Nutrition, Yantai Yuhuangding Hospital, Yantai, China

open access

Vol 75, No 1 (2024)
Original Paper
Submitted: 2023-05-11
Accepted: 2023-07-31
Published online: 2023-11-29

Abstract

Introduction: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients.

Material and methods: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways.

Results: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy.

Conclusions: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

Abstract

Introduction: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients.

Material and methods: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways.

Results: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy.

Conclusions: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

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Keywords

gestational diabetes mellitus; autophagy; Ambra1; IRS-1/PI3K/Akt

About this article
Title

sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes

Journal

Endokrynologia Polska

Issue

Vol 75, No 1 (2024)

Article type

Original paper

Pages

61-70

Published online

2023-11-29

Page views

381

Article views/downloads

456

DOI

10.5603/ep.95519

Pubmed

38497391

Bibliographic record

Endokrynol Pol 2024;75(1):61-70.

Keywords

gestational diabetes mellitus
autophagy
Ambra1
IRS-1/PI3K/Akt

Authors

Xin Qu
Xiao-yan Li
Yan Feng
Xiaoli Wang
Lei Li
Yu-ping Wang
Yong-li Chu

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