Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes
Z Wang, E Moro, K Kovacs, R Yu… - Proceedings of the …, 2003 - National Acad Sciences
Z Wang, E Moro, K Kovacs, R Yu, S Melmed
Proceedings of the National Academy of Sciences, 2003•National Acad SciencesThe mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister
chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression,
however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG−/−)
severely impairs glucose homeostasis leading to diabetes during late adulthood, especially
in males associated with nonautoimmune insulinopenia and reversed alpha/beta cell ratio.
Islet beta cell mass in PTTG−/− mice was already diminished before development of frank …
chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression,
however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG−/−)
severely impairs glucose homeostasis leading to diabetes during late adulthood, especially
in males associated with nonautoimmune insulinopenia and reversed alpha/beta cell ratio.
Islet beta cell mass in PTTG−/− mice was already diminished before development of frank …
The mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression, however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG−/−) severely impairs glucose homeostasis leading to diabetes during late adulthood, especially in males associated with nonautoimmune insulinopenia and reversed alpha/beta cell ratio. Islet beta cell mass in PTTG−/− mice was already diminished before development of frank diabetes and only increased minimally during growth. BrdUrd incorporation of islet cells in PTTG-null mice was ≈65% lower (P < 0.005) than in the WT pancreas, whereas apoptosis rates were similar. PTTG−/− beta cells had pleiotropic nuclei, suggesting defects in cell division. The results indicated that securin is indispensable for normal pancreatic beta cell proliferation.
National Acad Sciences