Frataxin deficiency in pancreatic islets causes diabetes due to loss of β cell mass
(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.
(Less)
- author
- organization
- publishing date
- 2003-08
- 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}}, }