RGD Reference Report - Absence of a reductase, NCB5OR, causes insulin-deficient diabetes. - Rat Genome Database

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Absence of a reductase, NCB5OR, causes insulin-deficient diabetes.

Authors: Xie, J  Zhu, H  Larade, K  Ladoux, A  Seguritan, A  Chu, M  Ito, S  Bronson, RT  Leiter, EH  Zhang, CY  Rosen, ED  Bunn, HF 
Citation: Xie J, etal., Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10750-5. Epub 2004 Jul 9.
RGD ID: 2315644
Pubmed: PMID:15247412   (View Abstract at PubMed)
PMCID: PMC490006   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0404044101   (Journal Full-text)

NCB5OR is a highly conserved NAD(P)H reductase that contains a cytochrome b5-like domain at the N terminus and a cytochrome b5 reductase-like domain at the C terminus. The enzyme is located in the endoplasmic reticulum (ER) and is widely expressed in organs and tissues. Targeted inactivation of this gene in mice has no impact on embryonic or fetal viability. At 4 weeks of age, Ncb5or-/- mice have normal blood glucose levels but impaired glucose tolerance. Isolated Ncb5or-/- islets have markedly impaired glucose- or arginine-stimulated insulin secretion. By 7 weeks of age, these mice develop severe hyperglycemia with markedly decreased serum insulin levels and nearly normal insulin tolerance. As the animals age, there is a progressive loss of beta cells in pancreatic islets, but there is no loss of alpha, delta, or PP cells. Electron microscopy reveals degranulation of beta cells and hypertrophic and hyperplastic mitochondria, some of which contain electron dense inclusions. Four-week-old Ncb5or-/- mice have enhanced sensitivity to the diabetogenic agent streptozotocin. NCB5OR appears to play a critical role in protecting pancreatic beta cells against oxidant stress.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetes mellitus  ISOCyb5r4 (Mus musculus)2315644; 2315644 RGD 
diabetes mellitus  IMP 2315644 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyb5r4  (cytochrome b5 reductase 4)

Genes (Mus musculus)
Cyb5r4  (cytochrome b5 reductase 4)

Genes (Homo sapiens)
CYB5R4  (cytochrome b5 reductase 4)


Additional Information