Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1
| Autor: | Shuyuan Chen, D R Wood, Paul A. Grayburn, C Yu, Jiahuan Ding, B Yang |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty endocrine system diseases medicine.medical_treatment Genetic enhancement Gene Expression Diabetes Mellitus Experimental Rats Sprague-Dawley Internal medicine Diabetes mellitus Genetics medicine Animals Insulin Ultrasonics Betacellulin Molecular Biology Pancreatic hormone Homeodomain Proteins geography Microbubbles geography.geographical_feature_category C-Peptide Reverse Transcriptase Polymerase Chain Reaction business.industry Genetic Therapy Glucagon Islet Streptozotocin medicine.disease Pancreas Exocrine Rats medicine.anatomical_structure Endocrinology Amylases Trans-Activators Intercellular Signaling Peptides and Proteins Molecular Medicine Pancreas business Biomarkers medicine.drug |
| Zdroj: | Gene Therapy. 14:1102-1110 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3302963 |
| Popis: | Ultrasound-targeted microbubble destruction (UTMD) was used to direct betacellulin (BTC) and pancreatic duodenal homeobox-1 (PDX1) to rat pancreas 48 h after islet destruction by streptozotocin (STZ). Sprague-Dawley rats were rendered diabetic by STZ injection. Controls included normal rats, STZ only without UTMD, and UTMD with DsRed reporter gene. Blood glucose increased dramatically in all rats 48 h after STZ, and continued to rise after UTMD with BTC alone. Blood glucose declined from day 3 to day 10 after UTMD with PDX1, but remained elevated (261+/-8 mg/dl). However, in rats treated with both BTC and PDX1, blood glucose remained below 200 mg/dl throughout day 10. This was accompanied by normalization of blood insulin and C-peptide. Histology demonstrated islet-like clusters of glucagon-staining cells in the rats treated with BTC and PDX1, but these clusters disappeared by 30 days after UTMD treatment. Although regeneration of insulin-producing islets was not seen, diabetes was reversed for up to 15 days after a single UTMD treatment by ectopic insulin production by pancreatic acinar cells. These cells co-expressed amylase and insulin and demonstrated several beta-cell markers by reverse transcription-PCR. Gene therapy by UTMD can reverse diabetes in vivo in adult rats by restoring pancreatic insulin production. |
| Databáze: | OpenAIRE |
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