Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology

Qiuyue Guo,1 Yunsheng Xu,2 Jie Li,3 Wenrong An,3 Dan Luo,4 Chengcheng Huang,4 Yanqin Huang4 1Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Endocrinology, Second Affiliated...

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Autores principales:	Guo Q, Xu Y, Li J, An W, Luo D, Huang C, Huang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	liraglutide type 2 diabetes mirna expression profile target gene signal pathway Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/41cde365294f49dca3b97a06abbd82ee
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spelling	oai:doaj.org-article:41cde365294f49dca3b97a06abbd82ee2021-12-02T16:34:31ZExplore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology1178-7007https://doaj.org/article/41cde365294f49dca3b97a06abbd82ee2021-09-01T00:00:00Zhttps://www.dovepress.com/explore-the-effect-and-target-of-liraglutide-on-islet-function-in-type-peer-reviewed-fulltext-article-DMSOhttps://doaj.org/toc/1178-7007Qiuyue Guo,1 Yunsheng Xu,2 Jie Li,3 Wenrong An,3 Dan Luo,4 Chengcheng Huang,4 Yanqin Huang4 1Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Endocrinology, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of China; 3First Clinical Medical College, Jingshi Rd. Campus, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Yanqin Huang Email huangyanqin2020@126.com; 20137125@sdutcm.deu.cnPurpose: To analyze the effect and potential therapeutic targets of liraglutide in type 2 diabetes through miRNA expression profiling.Methods: Ten of 30 SPF Wistar rats, males at 4 weeks old, were randomly selected as the control group and given conventional feed, the other rats adopted high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish a T2DM model. One unsuccessful rat was excluded, and the remaining rats were randomized to the model and the liraglutide group. Liraglutide group was subcutaneously injected with liraglutide 0.11 mg/kg for 8 weeks. The biochemical indicators and staining HE were detected. The expression of miRNA in pancreatic tissue was detected by miRNA sequencing. The intersection of miRNA difference was used to predict the target gene, then functional enrichment was performed to identify its possible biological functions and signal transduction paths. Finally, qRT-PCR was used to verify the results.Results: Compared to the model group, the level of fasting blood glucose (FBG), glucagon and insulin resistance index (HOMA-IR) in the liraglutide group were significantly decreased, fasting insulin (FINS) and insulin sensitivity index (ISI) were increased. Nine differential miRNAs (miR-135a-5p, miR-144-5p, miR-21-3p, miR-215, miR-451-5p, miR-486, miR-122-5p, miR-181d-5p and miR-345-5p) were identified at the intersection through two miRNA sequencing. A total of 3359 related target gene predictions were obtained. GO and pathway analyses demonstrated that differentially expressed genes were closely related to cell proliferation, angiogenesis, and proteolysis. Significant signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway.Conclusion: Liraglutide could improve islet function by regulating nine miRNAs, and the related signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Our study provided the basis and direction for further exploring the molecular mechanism of liraglutide on T2DM.Keywords: liraglutide, type 2 diabetes, miRNA expression profile, target gene, signaling pathwayGuo QXu YLi JAn WLuo DHuang CHuang YDove Medical Pressarticleliraglutidetype 2 diabetesmirna expression profiletarget genesignal pathwaySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 3795-3807 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liraglutide type 2 diabetes mirna expression profile target gene signal pathway Specialties of internal medicine RC581-951
spellingShingle	liraglutide type 2 diabetes mirna expression profile target gene signal pathway Specialties of internal medicine RC581-951 Guo Q Xu Y Li J An W Luo D Huang C Huang Y Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology
description	Qiuyue Guo,1 Yunsheng Xu,2 Jie Li,3 Wenrong An,3 Dan Luo,4 Chengcheng Huang,4 Yanqin Huang4 1Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Endocrinology, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of China; 3First Clinical Medical College, Jingshi Rd. Campus, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Yanqin Huang Email huangyanqin2020@126.com; 20137125@sdutcm.deu.cnPurpose: To analyze the effect and potential therapeutic targets of liraglutide in type 2 diabetes through miRNA expression profiling.Methods: Ten of 30 SPF Wistar rats, males at 4 weeks old, were randomly selected as the control group and given conventional feed, the other rats adopted high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish a T2DM model. One unsuccessful rat was excluded, and the remaining rats were randomized to the model and the liraglutide group. Liraglutide group was subcutaneously injected with liraglutide 0.11 mg/kg for 8 weeks. The biochemical indicators and staining HE were detected. The expression of miRNA in pancreatic tissue was detected by miRNA sequencing. The intersection of miRNA difference was used to predict the target gene, then functional enrichment was performed to identify its possible biological functions and signal transduction paths. Finally, qRT-PCR was used to verify the results.Results: Compared to the model group, the level of fasting blood glucose (FBG), glucagon and insulin resistance index (HOMA-IR) in the liraglutide group were significantly decreased, fasting insulin (FINS) and insulin sensitivity index (ISI) were increased. Nine differential miRNAs (miR-135a-5p, miR-144-5p, miR-21-3p, miR-215, miR-451-5p, miR-486, miR-122-5p, miR-181d-5p and miR-345-5p) were identified at the intersection through two miRNA sequencing. A total of 3359 related target gene predictions were obtained. GO and pathway analyses demonstrated that differentially expressed genes were closely related to cell proliferation, angiogenesis, and proteolysis. Significant signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway.Conclusion: Liraglutide could improve islet function by regulating nine miRNAs, and the related signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Our study provided the basis and direction for further exploring the molecular mechanism of liraglutide on T2DM.Keywords: liraglutide, type 2 diabetes, miRNA expression profile, target gene, signaling pathway
format	article
author	Guo Q Xu Y Li J An W Luo D Huang C Huang Y
author_facet	Guo Q Xu Y Li J An W Luo D Huang C Huang Y
author_sort	Guo Q
title	Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology
title_short	Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology
title_full	Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology
title_fullStr	Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology
title_full_unstemmed	Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology
title_sort	explore the effect and target of liraglutide on islet function in type 2 diabetic rats by mirna omics technology
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/41cde365294f49dca3b97a06abbd82ee
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Explore the Effect and Target of Liraglutide on Islet Function in Type 2 Diabetic Rats by miRNA Omics Technology

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