The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM

The glucagon-like peptide-1 (GLP-1) is a peptide with incretin activity and plays an important role in glycemic control as well as the improvement of insulin resistance in type 2 diabetes mellitus (T2DM). However, the short half-life of the native GLP-1 in circulation poses difficulties for clinical...

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Main Authors: Qing Wang, Haixin Guo, Wenwei Mao, Xiuping Qian, Yangang Liu
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/4/1202
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author Qing Wang
Haixin Guo
Wenwei Mao
Xiuping Qian
Yangang Liu
author_facet Qing Wang
Haixin Guo
Wenwei Mao
Xiuping Qian
Yangang Liu
author_sort Qing Wang
collection DOAJ
description The glucagon-like peptide-1 (GLP-1) is a peptide with incretin activity and plays an important role in glycemic control as well as the improvement of insulin resistance in type 2 diabetes mellitus (T2DM). However, the short half-life of the native GLP-1 in circulation poses difficulties for clinical practice. To improve the proteolytic stability and delivery properties of GLP-1, a protease-resistant modified GLP-1 (mGLP-1) was constructed with added arginine to ensure the structural integrity of the released mGLP-1 in vivo. The model probiotic <i>Lactobacillus plantarum</i> WCFS1 was chosen as the oral delivery vehicle with controllable endogenous genetic tools driven for mGLP-1 secretory constitutive expression. The feasibility of our design was explored in db/db mice which showed an improvement in diabetic symptoms related to decreased pancreatic glucagon, elevated pancreatic β-cell proportion, and increased insulin sensitivity. In conclusion, this study provides a novel strategy for the oral delivery of mGLP-1 and further probiotic transformation.
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spelling doaj.art-b86909f63c774bb9be35e13bb79d816d2023-11-17T20:54:10ZengMDPI AGPharmaceutics1999-49232023-04-01154120210.3390/pharmaceutics15041202The Oral Delivery System of Modified GLP-1 by Probiotics for T2DMQing Wang0Haixin Guo1Wenwei Mao2Xiuping Qian3Yangang Liu4School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaShanghai TriApex Biotechnology Co., Ltd., Shanghai 201315, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaThe glucagon-like peptide-1 (GLP-1) is a peptide with incretin activity and plays an important role in glycemic control as well as the improvement of insulin resistance in type 2 diabetes mellitus (T2DM). However, the short half-life of the native GLP-1 in circulation poses difficulties for clinical practice. To improve the proteolytic stability and delivery properties of GLP-1, a protease-resistant modified GLP-1 (mGLP-1) was constructed with added arginine to ensure the structural integrity of the released mGLP-1 in vivo. The model probiotic <i>Lactobacillus plantarum</i> WCFS1 was chosen as the oral delivery vehicle with controllable endogenous genetic tools driven for mGLP-1 secretory constitutive expression. The feasibility of our design was explored in db/db mice which showed an improvement in diabetic symptoms related to decreased pancreatic glucagon, elevated pancreatic β-cell proportion, and increased insulin sensitivity. In conclusion, this study provides a novel strategy for the oral delivery of mGLP-1 and further probiotic transformation.https://www.mdpi.com/1999-4923/15/4/1202type 2 diabetes mellitusGLP-1<i>Lactobacillus plantarum</i> WCFS1oral delivery
spellingShingle Qing Wang
Haixin Guo
Wenwei Mao
Xiuping Qian
Yangang Liu
The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM
Pharmaceutics
type 2 diabetes mellitus
GLP-1
<i>Lactobacillus plantarum</i> WCFS1
oral delivery
title The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM
title_full The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM
title_fullStr The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM
title_full_unstemmed The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM
title_short The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM
title_sort oral delivery system of modified glp 1 by probiotics for t2dm
topic type 2 diabetes mellitus
GLP-1
<i>Lactobacillus plantarum</i> WCFS1
oral delivery
url https://www.mdpi.com/1999-4923/15/4/1202
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