Journal article

Glucose Induces Pancreatic Islet Cell Apoptosis That Requires the BH3-Only Proteins Bim and Puma and Multi-BH Domain Protein Bax

Mark D McKenzie, Emma Jamieson, Elisa S Jansen, Clare L Scott, David CS Huang, Philippe Bouillet, Janette Allison, Thomas WH Kay, Andreas Strasser, Helen E Thomas



OBJECTIVE: High concentrations of circulating glucose are believed to contribute to defective insulin secretion and beta-cell function in diabetes and at least some of this effect appears to be caused by glucose-induced beta-cell apoptosis. In mammalian cells, apoptotic cell death is controlled by the interplay of proapoptotic and antiapoptotic members of the Bcl-2 family. We investigated the apoptotic pathway induced in mouse pancreatic islet cells after exposure to high concentrations of the reducing sugars ribose and glucose as a model of beta-cell death due to long-term metabolic stress. RESEARCH DESIGN AND METHODS: Islets isolated from mice lacking molecules implicated in cell death pat..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by National Institutes of Health

Awarded by Juvenile Diabetes Research Foundation/NHMRC


Funding Acknowledgements

This work was supported by fellowships and grants from the National Health and Medical Research Council of Australia (NHMRC) (NHMRC program 461221; NHMRC Career Development Awards to H.E.T. and C.L.S.; NHMRC Australia fellowship to A.S.), the National Institutes of Health (CA-043540-18 and CA-80188-6), and a joint special program grant from the Juvenile Diabetes Research Foundation/NHMRC (program 466658).No potential conflicts of interest relevant to this article were reported.We thank J.M. Adams, S. Cory, A. Villunger, and M. Labow for gene-targeted mice; M. Narita for qRT-PCR primers; G. Siciliano, N. lannarella, A. Gomes, and S. Fynch for animal care; and R. Ayala-Perez, B. Helbert, C. Youngadn, and C. Dobrzelak for technical assistance and genotyping.