Research Topics
Species | Jake A KushnerSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
Pdx1 restores beta cell function in Irs2 knockout miceJake A Kushner
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 109:1193-201. 2002..Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY...- Beta-cell growth: an unusual paradigm of organogenesis that is cyclin D2/Cdk4 dependentJake A Kushner
Children s Hospital of Philadelphia, Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Cell Cycle 5:234-7. 2006..This new paradigm of long-lived beta-cells challenges previous notions of rapid turnover of adult beta-cell mass. Thus, much remains to be learned in order to expand adult beta-cell mass in diabetes patients... - Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growthJake A Kushner
Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
Mol Cell Biol 25:3752-62. 2005..Thus, cyclins D2 and D1 were essential for beta-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in beta cells could prevent or cure diabetes... - Phosphatase and tensin homolog regulation of islet growth and glucose homeostasisJake A Kushner
Division of Endocrinology, Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 280:39388-93. 2005..Thus, steps to enhance phosphatidylinositol 3-kinase signaling can promote beta-cell growth, function, and survival without the Irs2 branch of the insulin/insulin-like growth factor signaling cascade... - Aging induces a distinct gene expression program in mouse isletsMatthew M Rankin
Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA USA
Islets 2:345-52. 2010..Taken together, our results reveal that aged islets exhibit a unique gene expression signature that could contribute to the limited regenerative capacity of mature β-cells... - Very slow turnover of beta-cells in aged adult miceMonica Teta
Division of Endocrinology, Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
Diabetes 54:2557-67. 2005..Although some pancreatic components acquired BrdU label in a linear fashion, only 1 in approximately 1,400 adult beta-cells were found to undergo replication per day. We conclude that adult beta-cells are very long lived... - Calcineurin signaling regulates human islet {beta}-cell survivalScott A Soleimanpour
Division of Endocrinology, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 285:40050-9. 2010..These findings reveal calcineurin as a regulator of human β-cell survival in part through regulation of Irs2, with implications for the pathogenesis and treatment of diabetes following organ transplantation... - Cyclin D2 protein stability is regulated in pancreatic beta-cellsLu Mei He
Division of Endocrinology and Diabetes, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Mol Endocrinol 23:1865-75. 2009.... - Growth and regeneration of adult beta cells does not involve specialized progenitorsMonica Teta
Division of Endocrinology, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Dev Cell 12:817-26. 2007..Our approach provides unbiased resolution of previously inaccessible developmental niches and can elucidate lineage mechanisms without candidate markers... - Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetesXueying Lin
Howard Hughes Medical Institute Children s Hospital, Division of Endocrinology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 114:908-16. 2004..Thus, Irs2 signaling promotes regeneration of adult beta cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice... - Adaptive beta-cell proliferation is severely restricted with advanced ageMatthew M Rankin
Division of Endocrinology and Diabetes, The Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Diabetes 58:1365-72. 2009..beta-Cell proliferation can be acutely stimulated by a variety of stimuli in young rodents. However, it is unknown whether this adaptive beta-cell regeneration capacity is retained into old age... - Overexpression of hepatocyte nuclear factor-4α initiates cell cycle entry, but is not sufficient to promote β-cell expansion in human isletsSebastian Rieck
Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, 12 126 Translational Research Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 5156, USA
Mol Endocrinol 26:1590-602. 2012..The DNA damage response is a barrier to efficient β-cell proliferation in vitro, and we suggest its evaluation in all attempts to stimulate β-cell replication as an approach to diabetes treatment... - Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animalsDorota B Pawlak
Department of Medicine, Children s Hospital, Boston, MA, USA
Lancet 364:778-85. 2004..This study examined the independent effects of GI in animals... - Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout miceJake A Kushner
Howard Hughes Medical Institute, Joslin Diabetes Center, and Division of Endocrinology, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 53:61-6. 2004..Our studies demonstrate a novel role for Ptp1b in regulating beta-cell homeostasis and indicate that Ptp1b deficiency can partially compensate for lack of Irs2... - Autoimmunity and beta cell regeneration in mouse and human type 1 diabetes: the peace is not enoughVitaly Ablamunits
Section of Immunobiology, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Ann N Y Acad Sci 1103:19-32. 2007..Additional therapeutic modalities capable of stimulating beta cell regeneration in the absence of active autoimmune destruction are urgently needed... - Identification of a WD40 repeat-containing isoform of PHIP as a novel regulator of beta-cell growth and survivalAlexey Podcheko
Department of Laboratory Medicine and Pathobiology, 1 King s College Circle, Room 6238, University of Toronto, Toronto, Canada M5S 1A8
Mol Cell Biol 27:6484-96. 2007..We suggest that PHIP1 may be involved in the induction of long-term gene expression programs to promote beta-cell mitogenesis and survival... - Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdUMark J Kiel
Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Centre for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
Nature 449:238-42. 2007..Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells... - Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cellsXianjin Yi
Howard Hughes Medical Institute, Children s Hospital Boston, Boston, Massachusetts 02115, USA
J Neurosci 25:1240-8. 2005.... - Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylationMarkus Schubert
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Neurosci 23:7084-92. 2003..Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease...