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Absence of a reductase, NCB5OR, causes insulin-deficient diabetes
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2004, 101 (29), pp.10750-5. ⟨10.1073/pnas.0404044101⟩
- Publication Year :
- 2004
- Publisher :
- Proceedings of the National Academy of Sciences, 2004.
-
Abstract
- 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.
- Subjects :
- Blood Glucose
Male
medicine.medical_treatment
MESH: Mice, Knockout
Impaired glucose tolerance
Mice
0302 clinical medicine
Homeostasis
Insulin
MESH: Animals
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Mice, Knockout
2. Zero hunger
0303 health sciences
Glucose tolerance test
Multidisciplinary
medicine.diagnostic_test
MESH: Glucagon
Biological Sciences
medicine.anatomical_structure
MESH: Homeostasis
Female
Oxidoreductases
Cytochrome-B(5) Reductase
medicine.drug
medicine.medical_specialty
MESH: Diabetes Mellitus
MESH: Glucose Tolerance Test
Mice, Inbred Strains
MESH: Insulin
Biology
MESH: Mice, Inbred Strains
Glucagon
Streptozocin
Islets of Langerhans
03 medical and health sciences
Internal medicine
Diabetes Mellitus
medicine
Animals
Humans
MESH: Oxidoreductases
MESH: Mice
030304 developmental biology
MESH: Humans
MESH: Islets of Langerhans
Pancreatic islets
Endoplasmic reticulum
MESH: Streptozocin
Glucose Tolerance Test
Streptozotocin
medicine.disease
MESH: Male
Endocrinology
MESH: Blood Glucose
MESH: Cytochrome-B(5) Reductase
MESH: Female
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....fe5d54e658c42bf0f4870636043ce20e