
Hindrik Mulder
Principal investigator

Frataxin deficiency in pancreatic islets causes diabetes due to loss of β cell mass
Author
Summary, in English
Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing β cells. We have disrupted expression of the mitochondrial protein frataxin selectively in pancreatic β cells. Mice were born healthy but subsequently developed impaired glucose tolerance progressing to overt diabetes mellitus. These observations were explained by impairment of insulin secretion due to a loss of β cell mass in knockout animals. This phenotype was preceded by elevated levels of reactive oxygen species in knockout islets, an increased frequency of apoptosis, and a decreased number of proliferating β cells. Hence, disruption of the frataxin gene in pancreatic β cells causes diabetes following cellular growth arrest and apoptosis, paralleled by an increase in reactive oxygen species in islets. These observations might provide insight into the deterioration of β cell function observed in different subtypes of diabetes in humans.
Department/s
- Diabetes - Molecular Metabolism
Publishing year
2003-08
Language
English
Pages
527-534
Publication/Series
Journal of Clinical Investigation
Volume
112
Issue
4
Document type
Journal article
Publisher
The American Society for Clinical Investigation
Topic
- Endocrinology and Diabetes
Status
Published
Research group
- Diabetes - Molecular Metabolism
ISBN/ISSN/Other
- ISSN: 0021-9738