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

Ristow, Michael ; Mulder, Hindrik LU orcid ; Pomplun, Doreen ; Schulz, Tim J. ; Müller-Schmehl, Katrin ; Krause, Anja ; Fex, Malin LU ; Puccio, Hélène ; Müller, Jörg and Isken, Frank , et al. (2003) In Journal of Clinical Investigation 112(4). p.527-534
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
112
issue
4
pages
527 - 534
publisher
The American Society for Clinical Investigation
external identifiers
  • scopus:85047690706
  • pmid:12925693
ISSN
0021-9738
DOI
10.1172/JCI18107
language
English
LU publication?
yes
additional info
Copyright: Copyright 2018 Elsevier B.V., All rights reserved.
id
2b9eca7a-c0c6-478f-93fa-832730d70db2
date added to LUP
2021-08-26 10:17:16
date last changed
2024-06-15 15:16:32
@article{2b9eca7a-c0c6-478f-93fa-832730d70db2,
  abstract     = {{<p>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.</p>}},
  author       = {{Ristow, Michael and Mulder, Hindrik and Pomplun, Doreen and Schulz, Tim J. and Müller-Schmehl, Katrin and Krause, Anja and Fex, Malin and Puccio, Hélène and Müller, Jörg and Isken, Frank and Spranger, Joachim and Müller-Wieland, Dirk and Magnuson, Mark A. and Möhlig, Matthias and Koenig, Michel and Pfeiffer, Andreas F.H.}},
  issn         = {{0021-9738}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{527--534}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{Journal of Clinical Investigation}},
  title        = {{Frataxin deficiency in pancreatic islets causes diabetes due to loss of β cell mass}},
  url          = {{http://dx.doi.org/10.1172/JCI18107}},
  doi          = {{10.1172/JCI18107}},
  volume       = {{112}},
  year         = {{2003}},
}