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- Ristow, Michael, et al.
(författare)
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Frataxin deficiency in pancreatic islets causes diabetes due to loss of β cell mass
- 2003
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 112:4, s. 527-534
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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