Oral delivery of a therapeutic gene encoding glucagon-like peptide 1 to treat high fat diet-induced diabetes.

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Journal of controlled release : official journal of the Controlled Release Society, ISSN: 1873-4995, Vol: 268, Page: 305-313

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Nurunnabi, Md; Lee, Seung-Ah; Revuri, Vishnu; Hwang, Yong Hwa; Kang, Sung Hun; Lee, Minhyung; Cho, Sungpil; Cho, Kwang Jae; Byun, Youngro; Bae, You Han; Lee, Dong Yun; Lee, Yong-Kyu Show More Hide
Elsevier BV
Pharmacology, Toxicology and Pharmaceutics
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article description
The number of people suffering from insulin-independent type 2 diabetes mellitus (T2DM) is ever increasing on a yearly basis. Current anti-diabetic medications often result in adverse weight gain and hypoglycemic episodes. Hypoglycemia can be avoided with glucagon-like peptide (GLP)-1 receptor agonists, which are expensive and require daily injections that may result immune activation. This study demonstrates the use of non-viral vector based oral delivery of GLP-1 gene through enterohepatic recycling pathways of bile acids. Oral administration of the plasmid DNA (pDNA) encoding GLP-1 decreased diabetic glucose levels to the normoglycemic range with significant weight reduction in a high-fat diet (HFD) induced diabetic mouse model and a genetically engineered T2DM rat model. This novel oral GLP1 delivery system is an attractive alternative to treat late-stage T2DM conditions that require repeated insulin injection and can potentially minimize the occurrence of hypoglycemic anomalies.