Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus

Chunjie Su,1 Qian Cheng,2 Liyun Wang2 1Department of Gastrointestinal Surgery, Jingmen No.1 People’s Hospital, Jingmen, 448000, People’s Republic of China; 2Department of Endocrinology, Yixing People’s Hospital, Yixing, 214200, Jiangsu, People’s Republic of Ch...

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Autores principales:	Su C, Cheng Q, Wang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	roux-en-y gastric bypass (rygb) hepatic glucose metabolism insulin resistance sirt1 irs1 mtor2 pkb Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/c4528091edc447b8a9b772907270111e
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spelling	oai:doaj.org-article:c4528091edc447b8a9b772907270111e2021-12-02T15:53:46ZRoux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus1178-7007https://doaj.org/article/c4528091edc447b8a9b772907270111e2021-05-01T00:00:00Zhttps://www.dovepress.com/roux-en-y-gastric-bypass-improves-hepatic-glucose-metabolism-involving-peer-reviewed-fulltext-article-DMSOhttps://doaj.org/toc/1178-7007Chunjie Su,1 Qian Cheng,2 Liyun Wang2 1Department of Gastrointestinal Surgery, Jingmen No.1 People’s Hospital, Jingmen, 448000, People’s Republic of China; 2Department of Endocrinology, Yixing People’s Hospital, Yixing, 214200, Jiangsu, People’s Republic of ChinaCorrespondence: Liyun WangDepartment of Endocrinology, Yixing People’s Hospital, No. 75, Tongzhenguan Road, Yicheng Street, Yixing, 214200, Jiangsu, People’s Republic of ChinaEmail wangliyunly@163.comBackground: Roux-en-Y gastric bypass (RYGB) is the most effective treatment for type 2 diabetes mellitus (T2DM). Previous studies have reported that silent information regulator 1 (Sirt1) closely relates to many pathological processes of glucose metabolism and insulin resistance (IR). However, it is unclear whether Sirt1 is involved in the hepatic glucose metabolism of T2DM after RYGB.Methods: T2DM rats were randomly divided into four groups: Control, DM, Diet and RYGB. Normal rats were served as the control group. Hematoxylin and eosin (H&E) staining and Masson staining assays were performed to explore the changes of liver fibrous tissue after RYGB. The effect of RYGB on the protein expression of Sirt1 was detected by the Western blotting assay and immunohistochemical assay. Next, we built the insulin resistance model of human hepatocyte cell lines (FL62891 and HHL5) using the human recombinant insulin. Western blotting assay was applied to determine the expression of Sirt1 and the expression change of IRS1/mTOR2 /PKB pathway-related proteins in FL62891 and HHL5 cells. Additionally, the effects of Sirt1 on the expression of PTP1B and FGF-21 in insulin-resistant FL62891 and HHL5 cells were investigated using Western blotting and immunofluorescence assay.Results: Our results showed that following RYGB improved the pathological changes of liver and increased the expression of Sirt1 in rats with T2DM compared with the diabetic rats. In experiments in vitro, the expression of Sirt1 was downregulated in insulin-resistance FL62891 and HHL5 cells. Moreover, overexpression of Sirt1 significantly increased the expression of FGF-21 whereas decreased the expression of PTP1B in insulin-resistance FL62891 and HHL5 cells. These above changes were alleviated in RYGB and Diet groups. Furthermore, RYGB could improve the glucose metabolism through activating IRS1/mTOR2/PKB pathways by regulating Sirt1 in rats with T2DM.Conclusion: RYGB could significantly improve hepatic glucose metabolism and increase the expression of Sirt1 in T2DM rats, which is related to the IRS1/mTOR2 /PKB pathway.Keywords: Roux-en-Y gastric bypass, RYGB, hepatic glucose metabolism, insulin resistance, Sirt1, IRS1, mTOR2, PKBSu CCheng QWang LDove Medical Pressarticleroux-en-y gastric bypass (rygb)hepatic glucose metabolisminsulin resistancesirt1irs1mtor2pkbSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 2269-2280 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	roux-en-y gastric bypass (rygb) hepatic glucose metabolism insulin resistance sirt1 irs1 mtor2 pkb Specialties of internal medicine RC581-951
spellingShingle	roux-en-y gastric bypass (rygb) hepatic glucose metabolism insulin resistance sirt1 irs1 mtor2 pkb Specialties of internal medicine RC581-951 Su C Cheng Q Wang L Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus
description	Chunjie Su,1 Qian Cheng,2 Liyun Wang2 1Department of Gastrointestinal Surgery, Jingmen No.1 People’s Hospital, Jingmen, 448000, People’s Republic of China; 2Department of Endocrinology, Yixing People’s Hospital, Yixing, 214200, Jiangsu, People’s Republic of ChinaCorrespondence: Liyun WangDepartment of Endocrinology, Yixing People’s Hospital, No. 75, Tongzhenguan Road, Yicheng Street, Yixing, 214200, Jiangsu, People’s Republic of ChinaEmail wangliyunly@163.comBackground: Roux-en-Y gastric bypass (RYGB) is the most effective treatment for type 2 diabetes mellitus (T2DM). Previous studies have reported that silent information regulator 1 (Sirt1) closely relates to many pathological processes of glucose metabolism and insulin resistance (IR). However, it is unclear whether Sirt1 is involved in the hepatic glucose metabolism of T2DM after RYGB.Methods: T2DM rats were randomly divided into four groups: Control, DM, Diet and RYGB. Normal rats were served as the control group. Hematoxylin and eosin (H&E) staining and Masson staining assays were performed to explore the changes of liver fibrous tissue after RYGB. The effect of RYGB on the protein expression of Sirt1 was detected by the Western blotting assay and immunohistochemical assay. Next, we built the insulin resistance model of human hepatocyte cell lines (FL62891 and HHL5) using the human recombinant insulin. Western blotting assay was applied to determine the expression of Sirt1 and the expression change of IRS1/mTOR2 /PKB pathway-related proteins in FL62891 and HHL5 cells. Additionally, the effects of Sirt1 on the expression of PTP1B and FGF-21 in insulin-resistant FL62891 and HHL5 cells were investigated using Western blotting and immunofluorescence assay.Results: Our results showed that following RYGB improved the pathological changes of liver and increased the expression of Sirt1 in rats with T2DM compared with the diabetic rats. In experiments in vitro, the expression of Sirt1 was downregulated in insulin-resistance FL62891 and HHL5 cells. Moreover, overexpression of Sirt1 significantly increased the expression of FGF-21 whereas decreased the expression of PTP1B in insulin-resistance FL62891 and HHL5 cells. These above changes were alleviated in RYGB and Diet groups. Furthermore, RYGB could improve the glucose metabolism through activating IRS1/mTOR2/PKB pathways by regulating Sirt1 in rats with T2DM.Conclusion: RYGB could significantly improve hepatic glucose metabolism and increase the expression of Sirt1 in T2DM rats, which is related to the IRS1/mTOR2 /PKB pathway.Keywords: Roux-en-Y gastric bypass, RYGB, hepatic glucose metabolism, insulin resistance, Sirt1, IRS1, mTOR2, PKB
format	article
author	Su C Cheng Q Wang L
author_facet	Su C Cheng Q Wang L
author_sort	Su C
title	Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus
title_short	Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus
title_full	Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus
title_fullStr	Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus
title_full_unstemmed	Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus
title_sort	roux-en-y gastric bypass improves hepatic glucose metabolism involving upregulation of sirt1 in type 2 diabetes mellitus
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/c4528091edc447b8a9b772907270111e
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Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus

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