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

Ristow, M; Mulder, Hindrik LU ; Pomplun, D; Schulz, T; Muller-Schmehl, K; Krause, A; Fex, Malin LU ; Puccio, H; Muller, J and Isken, F, 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 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... (More)
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. (Less)
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Contribution to journal
publication status
published
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in
Journal of Clinical Investigation
volume
112
issue
4
pages
527 - 534
publisher
The Journal of Clinical Investigation
external identifiers
  • pmid:12925693
  • wos:000184833900012
  • scopus:0141608617
ISSN
0021-9738
DOI
language
English
LU publication?
yes
id
70aa6df3-5680-4b9a-a0b1-d5851a54b41d (old id 303447)
date added to LUP
2007-09-20 17:44:55
date last changed
2018-06-17 04:54:02
@article{70aa6df3-5680-4b9a-a0b1-d5851a54b41d,
  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.},
  author       = {Ristow, M and Mulder, Hindrik and Pomplun, D and Schulz, T and Muller-Schmehl, K and Krause, A and Fex, Malin and Puccio, H and Muller, J and Isken, F and Spranger, J and Muller-Wieland, D and Magnuson, MA and Mohlig, M and Koenig, M and Pfeiffer, AFH},
  issn         = {0021-9738},
  language     = {eng},
  number       = {4},
  pages        = {527--534},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Frataxin deficiency in pancreatic islets causes diabetes due to loss of beta cell mass},
  url          = {http://dx.doi.org/},
  volume       = {112},
  year         = {2003},
}