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Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism

OBJECTIVE: To explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions. METHODS: We screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low...

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Autores principales: Hu, Hua, Zhao, Meng, Li, Zhaoyang, Nie, Hongli, He, Jia, Chen, Zhuo, Yuan, Jing, Guo, Huan, Zhang, Xiaomin, Yang, Handong, Wu, Tangchun, He, Meian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197112/
https://www.ncbi.nlm.nih.gov/pubmed/35712251
http://dx.doi.org/10.3389/fendo.2022.814347
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author Hu, Hua
Zhao, Meng
Li, Zhaoyang
Nie, Hongli
He, Jia
Chen, Zhuo
Yuan, Jing
Guo, Huan
Zhang, Xiaomin
Yang, Handong
Wu, Tangchun
He, Meian
author_facet Hu, Hua
Zhao, Meng
Li, Zhaoyang
Nie, Hongli
He, Jia
Chen, Zhuo
Yuan, Jing
Guo, Huan
Zhang, Xiaomin
Yang, Handong
Wu, Tangchun
He, Meian
author_sort Hu, Hua
collection PubMed
description OBJECTIVE: To explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions. METHODS: We screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low-abundance plasma proteins encoded by miR-193b-3p target genes were explored in this study population. We further investigated the potential cellular functions of the differentially expressed miRNAs in HepG2 cells. RESULTS: miR-193b-3p was differentially expressed in type 2 diabetes cases compared to healthy controls (fold change = 2.01, P = 0.006). Plasma levels of triosephosphate isomerase (TPI1, a protein involved in the glycolytic pathway) decreased in type 2 diabetes cases (fold change = 1.37, P = 0.002). The effect of miR-193b-3p on TPI1 was verified by transfection of miR-193b-3p into HepG2 cells. miR-193b-3p inhibited the expression of YWHAZ/14-3-3ζ in the PI3K-AKT pathway, subsequently altering the expression of FOXO1 and PCK1. After transfection, cells were incubated in glucose-free medium for another 4 h. Glucose levels in medium from cells with elevated miR-193b-3p levels were significantly higher than those in medium from negative control cells (P = 0.016). In addition, elevated miR-193b-3p reduced glucose uptake by inhibiting insulin receptor (IR) and GLUT2 expression. CONCLUSION: Plasma miR-193b-3p levels increased in type 2 diabetes cases, and TPI1 levels decreased in both plasma and HepG2 cells with increased miR-193b-3p levels, while extracellular lactate levels did not significantly changed. Moreover, miR-193b-3p may affect glucose metabolism by directly targeting YWHAZ/14-3-3ζ and upregulating the transcription factor FOXO1 downstream of the PI3K-AKT pathway.
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spelling pubmed-91971122022-06-15 Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism Hu, Hua Zhao, Meng Li, Zhaoyang Nie, Hongli He, Jia Chen, Zhuo Yuan, Jing Guo, Huan Zhang, Xiaomin Yang, Handong Wu, Tangchun He, Meian Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: To explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions. METHODS: We screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low-abundance plasma proteins encoded by miR-193b-3p target genes were explored in this study population. We further investigated the potential cellular functions of the differentially expressed miRNAs in HepG2 cells. RESULTS: miR-193b-3p was differentially expressed in type 2 diabetes cases compared to healthy controls (fold change = 2.01, P = 0.006). Plasma levels of triosephosphate isomerase (TPI1, a protein involved in the glycolytic pathway) decreased in type 2 diabetes cases (fold change = 1.37, P = 0.002). The effect of miR-193b-3p on TPI1 was verified by transfection of miR-193b-3p into HepG2 cells. miR-193b-3p inhibited the expression of YWHAZ/14-3-3ζ in the PI3K-AKT pathway, subsequently altering the expression of FOXO1 and PCK1. After transfection, cells were incubated in glucose-free medium for another 4 h. Glucose levels in medium from cells with elevated miR-193b-3p levels were significantly higher than those in medium from negative control cells (P = 0.016). In addition, elevated miR-193b-3p reduced glucose uptake by inhibiting insulin receptor (IR) and GLUT2 expression. CONCLUSION: Plasma miR-193b-3p levels increased in type 2 diabetes cases, and TPI1 levels decreased in both plasma and HepG2 cells with increased miR-193b-3p levels, while extracellular lactate levels did not significantly changed. Moreover, miR-193b-3p may affect glucose metabolism by directly targeting YWHAZ/14-3-3ζ and upregulating the transcription factor FOXO1 downstream of the PI3K-AKT pathway. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9197112/ /pubmed/35712251 http://dx.doi.org/10.3389/fendo.2022.814347 Text en Copyright © 2022 Hu, Zhao, Li, Nie, He, Chen, Yuan, Guo, Zhang, Yang, Wu and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Hu, Hua
Zhao, Meng
Li, Zhaoyang
Nie, Hongli
He, Jia
Chen, Zhuo
Yuan, Jing
Guo, Huan
Zhang, Xiaomin
Yang, Handong
Wu, Tangchun
He, Meian
Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
title Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
title_full Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
title_fullStr Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
title_full_unstemmed Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
title_short Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism
title_sort plasma mir-193b-3p is elevated in type 2 diabetes and could impair glucose metabolism
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197112/
https://www.ncbi.nlm.nih.gov/pubmed/35712251
http://dx.doi.org/10.3389/fendo.2022.814347
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