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Dyrk1a haploinsufficiency induces diabetes in mice through decreased pancreatic beta cell mass
Ist Teil von
Diabetologia, 2014-05, Vol.57 (5), p.960-969
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2014
Quelle
MEDLINE
Beschreibungen/Notizen
Aims/hypothesis
Growth factors and nutrients are important regulators of pancreatic beta cell mass and function. However, the signalling pathways by which these factors modulate these processes have not yet been fully elucidated. DYRK1A (also named minibrain/MNB) is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family that has been conserved across evolution. A significant amount of data implicates DYRK1A in brain growth and function, as well as in neurodegenerative processes in Alzheimer’s disease and Down’s syndrome. We investigated here whether DYRK1A would be an attractive candidate for beta cell growth modulation.
Methods
To study the role of DYRK1A in beta cell growth, we used
Dyrk1a
-deficient mice.
Results
We show that DYRK1A is expressed in pancreatic islets and provide evidence that changes in
Dyrk1a
gene dosage in mice strongly modulate glycaemia and circulating insulin levels. Specifically,
Dyrk1a
-haploinsufficient mice show severe glucose intolerance, reduced beta cell mass and decreased beta cell proliferation.
Conclusions/interpretation
Taken together, our data indicate that DYRK1A is a critical kinase for beta cell growth as
Dyrk1a
-haploinsufficient mice show a diabetic profile.