RGD Reference Report - Remission of diabetes by beta-cell regeneration in diabetic mice treated with a recombinant adenovirus expressing betacellulin. - Rat Genome Database

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Remission of diabetes by beta-cell regeneration in diabetic mice treated with a recombinant adenovirus expressing betacellulin.

Authors: Shin, S  Li, N  Kobayashi, N  Yoon, JW  Jun, HS 
Citation: Shin S, etal., Mol Ther. 2008 May;16(5):854-61. Epub 2008 Mar 18.
RGD ID: 2306965
Pubmed: PMID:18388935   (View Abstract at PubMed)
DOI: DOI:10.1038/mt.2008.22   (Journal Full-text)

Type 1 diabetes results from destruction of the majority of the pancreatic beta cells by beta cell-specific autoimmune responses; therefore, expansion of the beta-cell mass in vivo is a possible approach to its treatment. Betacellulin (BTC) is known to promote beta-cell growth and differentiation. We investigated whether transient, constitutive expression, and secretion of BTC would regenerate sufficient numbers of pancreatic beta cells to restore normoglycemia in diabetic animals. We constructed a recombinant adenoviral vector (rAd-BTC) containing the cytomegalovirus promoter/enhancer, beta-globin chimeric intron, and albumin leader sequence to facilitate secretion, followed by BTC (1-80) complementary DNA (cDNA) encoding mature BTC. A single intravenous (i.v.) administration of rAd-BTC resulted in complete remission of streptozotocin (STZ)-induced diabetes within 2 weeks in mice. The mice remained normoglycemic for >100 days; glucose tolerance tests showed kinetics similar to normal, nondiabetic mice. Pancreatic insulin content, beta-cell mass, and serum insulin levels in rAd-BTC-treated mice were significantly higher than in the controls. Treatment of autoimmune diabetic mice with rAd-BTC in combination with an immune suppressor resulted in remission of diabetes. We conclude that transient expression of BTC by rAd-BTC administration results in prolonged remission of diabetes in mice, by the regeneration of sufficient numbers of beta cells in the pancreas.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  IMP 2306965 RGD 
Experimental Diabetes Mellitus  ISOBTC (Homo sapiens)2306965; 2306965 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Btc  (betacellulin)

Genes (Mus musculus)
Btc  (betacellulin, epidermal growth factor family member)

Genes (Homo sapiens)
BTC  (betacellulin)


Additional Information