RGD Reference Report - Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1. - Rat Genome Database

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Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1.

Authors: Chen, S  Ding, J  Yu, C  Yang, B  Wood, DR  Grayburn, PA 
Citation: Chen S, etal., Gene Ther. 2007 Jul;14(14):1102-10. Epub 2007 Apr 26.
RGD ID: 2311224
Pubmed: PMID:17460716   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.gt.3302963   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDX1HumanExperimental Diabetes Mellitus  ISOPdx1 (Rattus norvegicus) RGD 
Pdx1RatExperimental Diabetes Mellitus  IMP  RGD 
Pdx1MouseExperimental Diabetes Mellitus  ISOPdx1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Mus musculus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Homo sapiens)
PDX1  (pancreatic and duodenal homeobox 1)


Additional Information