TY  - JOUR
AB  - On 11 January 1922 insulin injection was used for the first time in the treatment of diabetes. Even today, daily insulin injections are the life-saving treatment for patients with Type 1 diabetes and advanced Type 2 diabetes. However, insulin injections often fail to achieve full glucose control, which in the long-term leads to multiple complications and mortality. Beta-cells, the natural producers and secretors of insulin, remain the gold-standard in regulating blood glucose levels. In this review, we focus on three strategies aiming at counteracting beta-cell loss in order to gain insulin independence: replacement, replication and protection. The three approaches, together termed as the triumvirate of beta-cell regeneration, may constitute the basis for a future cure for diabetes.
AU  - Singh, S.P.*
AU  - Ninov, N.
C1  - 54958
C2  - 45969
CY  - Po Box 1397, Bilbao, Bizkaia E-48080, Spain
SP  - 453-464
TI  - The triumvirate of beta-cell regeneration: Solutions and bottlenecks to curing diabetes.
JO  - Int. J. Dev. Biol.
VL  - 62
IS  - 6-8
PB  - Univ Basque Country Upv-ehu Press
PY  - 2018
SN  - 0214-6282
ER  - 

TY  - JOUR
AB  - Pitx3 is a bicoid-related homeodomain transcription factor critical for the development of the ocular lens, mesencephalic dopaminergic neurons and skeletal muscle. In humans, mutations in PITX3 are responsible for cataracts and anterior segment abnormalities of varying degree; polymorphisms are associated with Parkinson’s disease. In aphakia (ak) mice, two deletions in the promoter region of Pitx3 cause abnormal lens development. Here, we investigated systematically the role of Pitx3 in lens development including its molecular targets responsible for the ak phenotype. We have shown that ak lenses exhibit reduced proliferation and aberrant fiber cell differentiation. This was associated with loss of Foxe3 expression, complete absence of Prox1 expression, reduced expression of epsilon-tubulin and earlier expression of gamma-crystallin during lens development. Using EMSA and ChIP assays, we demonstrated that Pitx3 binds to an evolutionary conserved bicoid-binding site on the 5’-upstream region of Foxe3. Finally, Pitx3 binding to 5’-upstream region of Foxe3 increased transcriptional activity significantly in a cell-based reporter assay. Identification of Foxe3 as a transcriptional target of Pitx3 explains at least in part some of the phenotypic similarities of the ak and dyl mice (dysgenic lens, a Foxe3 allele). These findings enhance our understanding of the molecular cascades which subserve lens development.
AU  - Ahmad, N.
AU  - Aslam, M.
AU  - Münster, D.
AU  - Horsch, M.
AU  - Khan, M.A.
AU  - Carlsson, P.*
AU  - Beckers, J.
AU  - Graw, J.
C1  - 28556
C2  - 33446
CY  - Bilbao
SP  - 741-751
TI  - Pitx3 directly regulates Foxe3 during early lens development.
JO  - Int. J. Dev. Biol.
VL  - 57
IS  - 9-10
PB  - UBC Press
PY  - 2013
SN  - 0214-6282
ER  - 

TY  - JOUR
AU  - Graw, J.
C1  - 2157
C2  - 22108
SP  - 1031-1044
TI  - Congenital hereditary cataracts.
JO  - Int. J. Dev. Biol.
VL  - 48
PY  - 2004
SN  - 0214-6282
ER  -