Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes

Introduction Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency of insulin. This study aims to explore the mechanism of TGFB-induced factor homeobox 1 (TGIF1) in the glycolipid metabolism of mice with T2D.Research design and met...

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Main Authors: Yuchen Li, Li Tao, Shikai Wang, Fuyan Bai, Liping Zheng, Lijun Hou
Format: Article
Language:English
Published: BMJ Publishing Group 2025-01-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/13/1/e004509.full
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author Yuchen Li
Li Tao
Shikai Wang
Fuyan Bai
Liping Zheng
Lijun Hou
author_facet Yuchen Li
Li Tao
Shikai Wang
Fuyan Bai
Liping Zheng
Lijun Hou
author_sort Yuchen Li
collection DOAJ
description Introduction Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency of insulin. This study aims to explore the mechanism of TGFB-induced factor homeobox 1 (TGIF1) in the glycolipid metabolism of mice with T2D.Research design and methods Mice with T2D were induced by high-fat diet and low-dose streptozotocin (STZ) injection. After TGIF1 was overexpressed in mice with T2D, the weight was monitored. The levels of fasting plasma glucose, fasting serum insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured. Staining assays were performed to observe liver tissue pathology and lipid accumulation. Liver function and oxidative stress were measured. Palmitic acid (PA)-induced primary hepatocytes were used to establish cell models. After TGIF1 was overexpressed in the cells, cell viability, cellular glucose uptake and consumption, and intracellular glycogen content were detected. The expression of TGIF1, miR-106b-5p, and early growth response 2 (EGR2) was detected and their binding relationships were analyzed. Combined experiments were conducted to validate the mechanism.Results TGIF1 was downregulated in mice with T2D. TGIF1 overexpression reduced hyperglycemia and hyperlipidemia, improved insulin resistance, increased liver glycogen content, and attenuated lipid accumulation and glycolipid metabolism disorders in mice with T2D. TGIF1 was enriched on the miR-106b-5p promoter and promoted miR-106b-5p expression. miR-106b-5p inhibited EGR2 expression. miR-106b-5p inhibition or EGR2 overexpression partially reversed the alleviative effect of TGIF1 overexpression on glycolipid metabolism disorders.Conclusion TGIF1 reduces glycolipid metabolism disorders in mice with T2D through the miR-106b-5p/EGR2 axis.
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spelling doaj-art-625a42ac83844a318513ab80d882369c2025-01-23T09:40:15ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972025-01-0113110.1136/bmjdrc-2024-004509Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetesYuchen Li0Li Tao1Shikai Wang2Fuyan Bai3Liping Zheng4Lijun Hou5Harbin Medical University, Harbin, Heilongjiang, ChinaTaian Disabled Soldier’s Hospital of Shandong Province, Tai`an, Shandong, ChinaThe Second Affiliated Hospital of Shandong First Medical University, Tai`an, Shandong, ChinaThe Second Affiliated Hospital of Shandong First Medical University, Tai`an, Shandong, ChinaThe First People’s Hospital of Ningyang, Ningyang, ChinaThe Second Affiliated Hospital of Shandong First Medical University, Tai`an, Shandong, ChinaIntroduction Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency of insulin. This study aims to explore the mechanism of TGFB-induced factor homeobox 1 (TGIF1) in the glycolipid metabolism of mice with T2D.Research design and methods Mice with T2D were induced by high-fat diet and low-dose streptozotocin (STZ) injection. After TGIF1 was overexpressed in mice with T2D, the weight was monitored. The levels of fasting plasma glucose, fasting serum insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured. Staining assays were performed to observe liver tissue pathology and lipid accumulation. Liver function and oxidative stress were measured. Palmitic acid (PA)-induced primary hepatocytes were used to establish cell models. After TGIF1 was overexpressed in the cells, cell viability, cellular glucose uptake and consumption, and intracellular glycogen content were detected. The expression of TGIF1, miR-106b-5p, and early growth response 2 (EGR2) was detected and their binding relationships were analyzed. Combined experiments were conducted to validate the mechanism.Results TGIF1 was downregulated in mice with T2D. TGIF1 overexpression reduced hyperglycemia and hyperlipidemia, improved insulin resistance, increased liver glycogen content, and attenuated lipid accumulation and glycolipid metabolism disorders in mice with T2D. TGIF1 was enriched on the miR-106b-5p promoter and promoted miR-106b-5p expression. miR-106b-5p inhibited EGR2 expression. miR-106b-5p inhibition or EGR2 overexpression partially reversed the alleviative effect of TGIF1 overexpression on glycolipid metabolism disorders.Conclusion TGIF1 reduces glycolipid metabolism disorders in mice with T2D through the miR-106b-5p/EGR2 axis.https://drc.bmj.com/content/13/1/e004509.full
spellingShingle Yuchen Li
Li Tao
Shikai Wang
Fuyan Bai
Liping Zheng
Lijun Hou
Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes
BMJ Open Diabetes Research & Care
title Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes
title_full Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes
title_fullStr Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes
title_full_unstemmed Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes
title_short Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes
title_sort mechanism of tgif1 on glycolipid metabolism disorders in mice with type 2 diabetes
url https://drc.bmj.com/content/13/1/e004509.full
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