1060. An Efficient GLP-1 Expression System Using Two Step Transcription Amplification for Type 2 Diabetes Gene Therapy

Type 2 diabetes mellitus (T2DM) and other metabolic diseases are essential links in the structure of morbidity and mortality in the modern world. The accepted strategy for the correction of T2DM and insulin resistance is drug therapy aimed at delivering insulin from the outside, stimulating the secretion of own insulin and reducing the concentration of blood glucose. However, modern studies demonstrate a great potential for the use of gene therapy approaches for the correction of T2DM and insulin resistance. In the present review, the main variants of plasmid gene therapy of T2DM using the genes of adiponectin and type 1 glucagon-like peptide, as well as the main variants of viral gene therapy of T2DM using the genes of type 1 and leptin are considered. T2DM gene therapy is currently not ready to enter into routine clinical practice, but, subject to improvements in delivery systems, it can be a powerful link in combination therapy for diabetes.

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Advances and potential of gene therapy for type 2 diabetes mellitus

Biotechnology & Biotechnological Equipment ◽

10.1080/13102818.2019.1643783 ◽

2019 ◽

Vol 33 (1) ◽

pp. 1150-1157 ◽

Cited By ~ 1

Author(s):

Zonghao Yue ◽

Lijuan Zhang ◽

Chunyan Li ◽

Yanjuan Chen ◽

Yaping Tai ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Gene Therapy ◽

Type 2 Diabetes Mellitus

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The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis

Molecular Metabolism ◽

10.1016/j.molmet.2020.101015 ◽

2020 ◽

Vol 40 ◽

pp. 101015 ◽

Cited By ~ 1

Author(s):

Gaelle R. Carrat ◽

Elizabeth Haythorne ◽

Alejandra Tomas ◽

Leena Haataja ◽

Andreas Müller ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gene Product ◽

Secretory Granule ◽

Binding Protein ◽

Diabetes Gene ◽

Insulin Secretory Granule

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Engineered glucagon-like peptide-1-producing hepatocytes lower plasma glucose levels in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90768.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. E936-E944 ◽

Cited By ~ 9

Author(s):

Michael J. Riedel ◽

Corinna Wai Kwan Lee ◽

Timothy J. Kieffer

Keyword(s):

Type 2 Diabetes ◽

Gene Therapy ◽

Plasma Glucose ◽

Glucose Levels ◽

Dpp Iv ◽

Adenoviral Delivery ◽

Glucagon Like Peptide ◽

Novel Strategy

Glucagon-like peptide (GLP)-1 is an incretin hormone with well-characterized antidiabetic properties, including glucose-dependent stimulation of insulin secretion and enhancement of β-cell mass. GLP-1 agonists have recently been developed and are now in clinical use for the treatment of type 2 diabetes. Rapid degradation of GLP-1 by enzymes including dipeptidyl-peptidase (DPP)-IV and neutral endopeptidase (NEP) 24.11, along with renal clearance, contribute to a short biological half-life, necessitating frequent injections to maintain therapeutic efficacy. Gene therapy may represent a promising alternative approach for achieving long-term increases in endogenous release of GLP-1. We have developed a novel strategy for glucose-regulated production of GLP-1 in hepatocytes by expressing a DPP-IV-resistant GLP-1 peptide in hepatocytes under control of the liver-type pyruvate kinase promoter. Adenoviral delivery of this construct to hepatocytes in vitro resulted in production and secretion of bioactive GLP-1 as measured by a luciferase-based bioassay developed to detect the NH2-terminally modified GLP-1 peptide engineered for this study. Transplantation of encapsulated hepatocytes into CD-1 mice resulted in an increase in plasma GLP-1 levels that was accompanied by a significant reduction in fasting plasma glucose levels. The results from this study demonstrate that a gene therapy approach designed to induce GLP-1 production in hepatocytes may represent a novel strategy for long-term secretion of bioactive GLP-1 for the treatment of type 2 diabetes.

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Replication of recently described type 2 diabetes gene variants in a South Indian population

Metabolism ◽

10.1016/j.metabol.2010.04.024 ◽

2010 ◽

Vol 59 (12) ◽

pp. 1760-1766 ◽

Cited By ~ 32

Author(s):

Manickam Chidambaram ◽

Venkatesan Radha ◽

Viswanathan Mohan

Keyword(s):

Type 2 Diabetes ◽

Indian Population ◽

South Indian Population ◽

Gene Variants ◽

South Indian ◽

Diabetes Gene

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Generation of Dipeptidyl Peptidase-IV-Inhibiting Peptides fromβ-Lactoglobulin Secreted byLactococcus lactis

BioMed Research International ◽

10.1155/2014/393598 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Suguru Shigemori ◽

Kazushi Oshiro ◽

Pengfei Wang ◽

Yoshinari Yamamoto ◽

Yeqin Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Expression System ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Delivery Vehicle ◽

Dpp Iv

Previous studies showed that hydrolysates ofβ-lactoglobulin (BLG) prepared using gastrointestinal proteases strongly inhibit dipeptidyl peptidase-IV (DPP-IV) activityin vitro. In this study, we developed a BLG-secretingLactococcus lactisstrain as a delivery vehicle andin situexpression system. Interestingly, trypsin-digested recombinant BLG fromL. lactisinhibited DPP-IV activity, suggesting that BLG-secretingL. lactismay be useful in the treatment of type 2 diabetes mellitus.

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