Search Results
You are looking at 1 - 1 of 1 items for
- Author: Silke Erdmann x
- Refine by access: All content x
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Hannah J Welters in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Sabine Senkel in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Ludger Klein-Hitpass in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Silke Erdmann in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Heike Thomas in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Lorna W Harries in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Ewan R Pearson in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Coralie Bingham in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Andrew T Hattersley in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Gerhart U Ryffel in
Google Scholar
PubMed
Institut für Zellbiologie, Universitätsklinikum Essen, D-45122 Essen, Germany
Search for other papers by Noel G Morgan in
Google Scholar
PubMed
Mutations in the gene encoding hepatocyte nuclear factor (HNF)1β result in maturity-onset diabetes of the young-(MODY)5, by impairing insulin secretory responses and, possibly, by reducing β-cell mass. The functional role of HNF1β in normal β-cells is poorly understood; therefore, in the present study, wild-type (WT) HNF1β, or one of two naturally occurring MODY5 mutations (an activating mutation, P328L329del, or a dominant-negative form, A263insGG) were conditionally expressed in the pancreatic β-cell line, insulin-1 (INS-1), and the functional consequences examined. Surprisingly, overexpression of the dominant-negative mutant did not modify any of the functional properties of the cells studied (including insulin secretion, cell growth and viability). By contrast, expression of WT HNF1β was associated with a time- and dose-dependent inhibition of INS-1 cell proliferation and a marked increase in apoptosis. Induction of WT HNF1β also inhibited the insulin secretory response to nutrient stimuli, membrane depolarisation or activation of protein kinases A and C and this correlated with a significant decrease in pancrease-duodenum homeobox-1 protein levels. The attenuation of insulin secretion was, however, dissociated from the inhibition of proliferation and loss of viability, since expression of the P328L329del mutant led to a reduced rate of cell proliferation, but failed to induce apoptosis or to alter insulin secretion. Taken together, the present results suggest that mature rodent β-cells are sensitive to increased expression of WT HNF1β and they imply that the levels of this protein are tightly regulated to maintain secretory competence and cell viability.
