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van Buerck, L.* ; Schuster, M.* ; Rathkolb, B. ; Sabrautzki, S. ; Hrabě de Angelis, M. ; Wolf, E.* ; Aigner, B.* ; Wanke, R.* ; Herbach, N.*

Enhanced oxidative stress and endocrine pancreas alterations are linked to a novel glucokinase missense mutation in ENU-derived Munich GckD217V mutants.

Mol. Cell. Endocrinol. 362, 139-148 (2012)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
In the large-scale Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project murine models recapitulating human diseases were generated. In one strain, a novel missense mutation (D217V) in the glucokinase (Gck) gene was identified, resulting in decreased glucokinase activity. Heterozygous mutants display mild hyperglycaemia, disturbed glucose tolerance, and decreased glucose-induced insulin secretion. In contrast, homozygous mutants exhibit severe but not survival affecting hyperglycaemia, mild growth retardation, diminished oxidative capacity, and increased abundance of CHOP protein in the islets. Furthermore, the total islet and β-cell volumes and the total volume of isolated β-cells are significantly decreased in adult homozygous mutants, whereas in neonatal mice, β-cell mass is not yet significantly decreased and islet neogenesis is unaltered. Therefore, reduced total islet and β-cell volumes of adult homozygous mutants might predominantly emerge from disturbed postnatal islet neogenesis. Thus, we identified a novel Gck mutation in mice, with relevance in humans, leading to glycaemic disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Maturity-onset diabetes of the young, Neonatal diabetes; Glucokinase; β-cell dysfunction; ENU; Experimental genetics; Beta-Cell Glucokinase; Dependent Diabetes-Mellitus; Glucose-Homeostasis; Nitrosourea Mutagenesis; Insulin-Secretion; Protein Stability; Genome-Wide; Mouse Model; Gene; Young
ISSN (print) / ISBN 0303-7207
e-ISSN 1872-8057
Zeitschrift Molecular and Cellular Endocrinology
Quellenangaben Band: 362, Heft: 1-2, Seiten: 139-148 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Shannon
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)