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

Abstract
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.
AuthorsMd Nurunnabi, Seung-Ah Lee, Vishnu Revuri, Yong Hwa Hwang, Sung Hun Kang, Minhyung Lee, Sungpil Cho, Kwang Jae Cho, Youngro Byun, You Han Bae, Dong Yun Lee, Yong-Kyu Lee
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 268 Pg. 305-313 (Dec 28 2017) ISSN: 1873-4995 [Electronic] Netherlands
PMID28860072 (Publication Type: Journal Article)
CopyrightCopyright © 2017. Published by Elsevier B.V.
Chemical References
  • Taurocholic Acid
  • Glucagon-Like Peptide 1
  • Heparin
  • DNA
Topics
  • Animals
  • Cell Line
  • DNA (administration & dosage, chemistry)
  • Diabetes Mellitus, Type 2 (therapy)
  • Diet, High-Fat
  • Female
  • Gene Transfer Techniques
  • Genetic Therapy
  • Glucagon-Like Peptide 1 (genetics)
  • Heparin (administration & dosage, chemistry)
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Rats, Sprague-Dawley
  • Rats, Zucker
  • Taurocholic Acid (administration & dosage, chemistry)

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