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.
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-haploinsufficientmice 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-haploinsufficientmice show a diabetic profile.
Authors: Barbara Hämmerle; Edgar Ulin; Jordi Guimera; Walter Becker; François Guillemot; Francisco J Tejedor Journal: Development Date: 2011-06 Impact factor: 6.868
Authors: Yassan Abdolazimi; Zhengshan Zhao; Sooyeon Lee; Haixia Xu; Paul Allegretti; Timothy M Horton; Benjamin Yeh; Hannah P Moeller; Robert J Nichols; David McCutcheon; Aryaman Shalizi; Mark Smith; Neali A Armstrong; Justin P Annes Journal: Endocrinology Date: 2018-09-01 Impact factor: 4.736
Authors: Jianling Ji; Hane Lee; Bob Argiropoulos; Naghmeh Dorrani; John Mann; Julian A Martinez-Agosto; Natalia Gomez-Ospina; Natalie Gallant; Jonathan A Bernstein; Louanne Hudgins; Leah Slattery; Bertrand Isidor; Cédric Le Caignec; Albert David; Ewa Obersztyn; Barbara Wiśniowiecka-Kowalnik; Michelle Fox; Joshua L Deignan; Eric Vilain; Emily Hendricks; Margaret Horton Harr; Sarah E Noon; Jessi R Jackson; Alisha Wilkens; Ghayda Mirzaa; Noriko Salamon; Jeff Abramson; Elaine H Zackai; Ian Krantz; A Micheil Innes; Stanley F Nelson; Wayne W Grody; Fabiola Quintero-Rivera Journal: Eur J Hum Genet Date: 2015-05-06 Impact factor: 4.246