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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Frataxin deficiency in pancreatic islets causes diabetes due to loss of β cell mass

Author

  • Michael Ristow
  • Hindrik Mulder
  • Doreen Pomplun
  • Tim J. Schulz
  • Katrin Müller-Schmehl
  • Anja Krause
  • Malin Fex
  • Hélène Puccio
  • Jörg Müller
  • Frank Isken
  • Joachim Spranger
  • Dirk Müller-Wieland
  • Mark A. Magnuson
  • Matthias Möhlig
  • Michel Koenig
  • Andreas F.H. Pfeiffer

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

Am Soc Clin Investig

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Molecular Metabolism

ISBN/ISSN/Other

  • ISSN: 0021-9738