title: Frataxin deficiency in pancreatic islets causes diabetes due to loss of beta cell mass.
abstract: Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing beta cells. We have disrupted expression of the mitochondrial protein frataxin selectively in pancreatic beta 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 beta 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 beta cells. Hence, disruption of the frataxin gene in pancreatic beta 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 beta cell function observed in different subtypes of diabetes in humans.
authors.affiliation: German Institute of Human Nutrition, Department Klinische Ernährung, 114 Arthur-Scheunert-Strasse, D-14558 Bergholz-Rehbrücke, Germany. mristow@mristow.org
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.forename: Hindrik
authors.initials: H
authors.lastname: Mulder
authors.forename: Doreen
authors.initials: D
authors.lastname: Pomplun
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schulz
authors.forename: Katrin
authors.initials: K
authors.lastname: Müller-Schmehl
authors.forename: Anja
authors.initials: A
authors.lastname: Krause
authors.forename: Malin
authors.initials: M
authors.lastname: Fex
authors.forename: Helene
authors.initials: H
authors.lastname: Puccio
authors.forename: Jörg
authors.initials: J
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Isken
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller-Wieland
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: Matthias
authors.initials: M
authors.lastname: Möhlig
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D018076:DNA, Complementary / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D005091:Exons; D005838:Genotype; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008280:Magnetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D017382:Reactive Oxygen Species; D013997:Time Factors; D014018:Tissue Distribution; D000096923:Frataxin
chemical_list: D018076:DNA, Complementary; D007328:Insulin; D033862:Iron-Binding Proteins; D017382:Reactive Oxygen Species; D000096923:Frataxin