D Accili

Summary

Affiliation: Columbia University
Country: USA

Publications

  1. pmc The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression
    J Nakae
    Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Clin Invest 108:1359-67. 2001
  2. pmc Regulation of insulin-like growth factor-dependent myoblast differentiation by Foxo forkhead transcription factors
    Marta L Hribal
    Russ Berrie Research Pavilion, Rm 238, 1150 St Nicholas Avenue, New York, NY 10032, USA
    J Cell Biol 162:535-41. 2003
  3. pmc Foxo1 links hyperglycemia to LDL oxidation and endothelial nitric oxide synthase dysfunction in vascular endothelial cells
    Jun Tanaka
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    Diabetes 58:2344-54. 2009
  4. pmc Diabetes in mice with selective impairment of insulin action in Glut4-expressing tissues
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 60:700-9. 2011
  5. pmc InsR/FoxO1 signaling curtails hypothalamic POMC neuron number
    Leona Plum
    Naomi Berrie Diabetes Center, Department of Medicine, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 7:e31487. 2012
  6. pmc Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner
    Utpal B Pajvani
    Department of Medicine, Columbia University, New York, New York, USA
    Nat Med 17:961-7. 2011
  7. pmc Generation of functional insulin-producing cells in the gut by Foxo1 ablation
    Chutima Talchai
    Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA
    Nat Genet 44:406-12, S1. 2012
  8. pmc Functional characterization of the matrix metalloproteinase-1 cigarette smoke-responsive region and association with the lung health study
    Alison M Wallace
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Respir Res 13:79. 2012
  9. pmc Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center, 1150 St Nicholas Ave, Russ Berrie Pavilion Room 238, NY 10032, USA
    Circ Res 112:992-1003. 2013
  10. ncbi Metabolic diapause in pancreatic beta-cells expressing a gain-of-function mutant of the forkhead protein Foxo1
    Jean Buteau
    Berrie Diabetes Center, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA
    J Biol Chem 282:287-93. 2007

Research Grants

  1. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2010
  2. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2010
  3. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2005
  4. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2006
  5. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2007
  6. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2007
  7. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2009
  8. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2009
  9. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2005
  10. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2003

Detail Information

Publications83

  1. pmc The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression
    J Nakae
    Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Clin Invest 108:1359-67. 2001
    ..These findings are consistent with the possibility that Foxo1 is involved in insulin regulation of glucose production by mediating the ability of insulin to decrease the glucocorticoid/cAMP response of G6p...
  2. pmc Regulation of insulin-like growth factor-dependent myoblast differentiation by Foxo forkhead transcription factors
    Marta L Hribal
    Russ Berrie Research Pavilion, Rm 238, 1150 St Nicholas Avenue, New York, NY 10032, USA
    J Cell Biol 162:535-41. 2003
    ..Inhibition of Foxo expression by siRNA resulted in more efficient differentiation, associated with increased myosin expression. These observations indicate that Foxo proteins are key effectors of Akt-dependent myogenesis...
  3. pmc Foxo1 links hyperglycemia to LDL oxidation and endothelial nitric oxide synthase dysfunction in vascular endothelial cells
    Jun Tanaka
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    Diabetes 58:2344-54. 2009
    ..Biochemical mechanism leading from hyperglycemia to oxLDL formation and eNOS dysfunction is unknown...
  4. pmc Diabetes in mice with selective impairment of insulin action in Glut4-expressing tissues
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 60:700-9. 2011
    ..We hypothesized that diabetes is the result of impaired insulin signaling in all Glut4-expressing tissues...
  5. pmc InsR/FoxO1 signaling curtails hypothalamic POMC neuron number
    Leona Plum
    Naomi Berrie Diabetes Center, Department of Medicine, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 7:e31487. 2012
    ..These changes in Pomc cells occurred in the absence of marked changes in humoral factors or hypothalamic NPY neurons...
  6. pmc Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner
    Utpal B Pajvani
    Department of Medicine, Columbia University, New York, New York, USA
    Nat Med 17:961-7. 2011
    ..The data identify a heretofore unknown metabolic function of Notch and suggest that Notch inhibition is beneficial in diabetes treatment, in part by helping to offset excessive FoxO1-driven hepatic glucose production...
  7. pmc Generation of functional insulin-producing cells in the gut by Foxo1 ablation
    Chutima Talchai
    Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA
    Nat Genet 44:406-12, S1. 2012
    ..The data indicate that Neurog3(+) enteroendocrine progenitors require active Foxo1 to prevent differentiation into Ins(+) cells. Foxo1 ablation in gut epithelium may provide an approach to restore insulin production in type 1 diabetes...
  8. pmc Functional characterization of the matrix metalloproteinase-1 cigarette smoke-responsive region and association with the lung health study
    Alison M Wallace
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Respir Res 13:79. 2012
    ..Prior studies have demonstrated that the distal 1.5 kb of the MMP-1 promoter is fundamental in directing the induction of the MMP-1 gene by cigarette smoke...
  9. pmc Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice
    Kyoichiro Tsuchiya
    Naomi Berrie Diabetes Center, 1150 St Nicholas Ave, Russ Berrie Pavilion Room 238, NY 10032, USA
    Circ Res 112:992-1003. 2013
    ..Increased neutrophil and monocyte counts are often associated with an increased risk of atherosclerosis, but their relationship to insulin sensitivity is unknown...
  10. ncbi Metabolic diapause in pancreatic beta-cells expressing a gain-of-function mutant of the forkhead protein Foxo1
    Jean Buteau
    Berrie Diabetes Center, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA
    J Biol Chem 282:287-93. 2007
    ..We propose the definition of "metabolic diapause" for the changes induced by Foxo1 to protect beta-cells against oxidative stress. The data provide genetic underpinning for the concept of beta-cell rest as a treatment goal in diabetes...
  11. pmc Homozygosity for an allele encoding deacetylated FoxO1 protects macrophages from cholesterol-induced inflammation without increasing apoptosis
    Kyoichiro Tsuchiya
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Arterioscler Thromb Vasc Biol 31:2920-8. 2011
    ..We sought to identify the mechanism whereby FoxO1 dampens inflammation without promoting apoptosis. We hypothesized that nutrient-dependent FoxO1 acetylation plays a role in this process...
  12. ncbi FoxOs at the crossroads of cellular metabolism, differentiation, and transformation
    Domenico Accili
    College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell 117:421-6. 2004
    ..The gamut of phenotypes runs from protection against diabetes and predisposition to neoplasia, conferred by FoxO loss of function, to increased cellular survival and a marked catabolic response associated with gain of function...
  13. ncbi Genetics of type 2 diabetes: insight from targeted mouse mutants
    D Accili
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Curr Mol Med 1:9-23. 2001
    ..Here we review recent progress in the field and assess its impact on human studies of the genetics, prevention and treatment of type 2 diabetes...
  14. pmc Divergent regulation of energy expenditure and hepatic glucose production by insulin receptor in agouti-related protein and POMC neurons
    Hua V Lin
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 59:337-46. 2010
    ..We have shown that mice with hypothalamic deficiency (L1) of insulin receptors (InsRs) fail to regulate hepatic glucose production (HGP) in response to insulin...
  15. ncbi Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic
    Domenico Accili
    Department of Medicine, Naomi Berrie Diabetes Center, College of Physicians and Surgeons of Columbia University, Columbia University, New York, NY, USA
    Diabetes 53:1633-42. 2004
    ..I propose that we replace the original picture of a ruling triumvirate with that of a squabbling republic in which every tissue contributes to the onset of the disease...
  16. ncbi A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance
    J C Bruning
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 2:559-69. 1998
    ..Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized...
  17. ncbi Clinical review 125: The insulin receptor and its cellular targets
    Y Kido
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Endocrinol Metab 86:972-9. 2001
    ..The ultimate goal of these investigations is to provide clues to the pathogenesis and treatment of the insulin resistant state that is characteristic of type 2 diabetes...
  18. ncbi The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells
    Masayuki Adachi
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    Gastroenterology 132:1434-46. 2007
    ..Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. A fibrotic stimulus causes HSCs to transdifferentiate from a quiescent phenotype to a collagen-producing myofibroblast-like phenotype and to proliferate...
  19. ncbi Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt
    J Nakae
    Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Biochemistry 40:11768-76. 2001
    ..These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase...
  20. ncbi Mitogenic and metabolic effects of type I IGF receptor overexpression in insulin receptor-deficient hepatocytes
    J J Kim
    Naomi Berrie Diabetes Center and Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Endocrinology 142:3354-60. 2001
    ..The data are consistent with the possibility that there exist intrinsic signaling differences between insulin and IGF-I receptors...
  21. pmc Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans
    Alexander S Banks
    Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Clin Invest 115:2462-71. 2005
    ..Additionally, SOCS7 associated with the INSR and IRS1--molecules that are essential for normal regulation of insulin action. These data suggest that SOCS7 is a potent regulator of glucose homeostasis and insulin signaling...
  22. ncbi Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1
    Jun Nakae
    Naomi Berrie Diabetes Center, Berrie Research Pavilion, 1150 St Nicholas Avenue, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Nat Genet 32:245-53. 2002
    ..This has been corrected in the full-text online version of the article. The name will appear correctly in the print version...
  23. ncbi FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction
    Yukari Ido Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New York, New York 10032, USA
    Cell Metab 2:153-63. 2005
    ..The findings provide a mechanism linking glucose- and growth factor receptor-activated pathways to protect beta cells against oxidative damage via FoxO proteins...
  24. pmc Mosaic analysis of insulin receptor function
    Tadahiro Kitamura
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Clin Invest 113:209-19. 2004
    ..These findings indicate that insulin regulates growth independently of metabolism and that the number of insulin receptors is an important determinant of the specificity of insulin action...
  25. pmc Transgenic rescue of insulin receptor-deficient mice
    Haruka Okamoto
    Department of Medicine, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Clin Invest 114:214-23. 2004
    ..These data indicate, surprisingly, that insulin receptor signaling in noncanonical insulin target tissues is sufficient to maintain fuel homeostasis and prevent diabetes...
  26. pmc Preserved pancreatic beta-cell development and function in mice lacking the insulin receptor-related receptor
    T Kitamura
    Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Mol Cell Biol 21:5624-30. 2001
    ..We conclude that glucose-stimulated insulin secretion and embryonic beta-cell development occur normally in mice lacking Irr...
  27. ncbi Distinct and overlapping functions of insulin and IGF-I receptors
    J Nakae
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Endocr Rev 22:818-35. 2001
    ..The phenotypes of insulin receptor gene mutations in humans and in mice indicate important differences between the developmental roles of insulin and its receptor in the two species...
  28. ncbi In vivo mutagenesis of the insulin receptor
    Haruka Okamoto
    Department of Medicine and Institute of Human Nutrition, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Biol Chem 278:28359-62. 2003
    ....
  29. ncbi Effects of mutations in the insulin-like growth factor signaling system on embryonic pancreas development and beta-cell compensation to insulin resistance
    Yoshiaki Kido
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 277:36740-7. 2002
    ..We conclude that Igf1r and Insr are required for embryonic development of the exocrine but not of the endocrine pancreas and that defects of Igf1r do not alter glucose homeostasis as long as the insulin receptor system remains intact...
  30. ncbi Adiponectin resistance exacerbates insulin resistance in insulin receptor transgenic/knockout mice
    Hua V Lin
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Diabetes 56:1969-76. 2007
    ..Adiponectin increases insulin sensitivity and contributes to insulin's indirect effects on hepatic glucose production...
  31. pmc Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant macrophages during cholesterol-induced endoplasmic reticulum stress
    Takafumi Senokuchi
    Department of Medicine, Columbia University, New York, New York, USA
    Diabetes 57:2967-76. 2008
    ..However, the molecular mechanisms of increased apoptosis in insulin-resistant macrophages remain unclear...
  32. ncbi Genetic and biochemical pathways of beta-cell failure in type 2 diabetes
    C Talchai
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Diabetes Obes Metab 11:38-45. 2009
    ....
  33. pmc Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR
    J Nakae
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    EMBO J 19:989-96. 2000
    ..We propose that site-specific phosphorylation of FKHR is one of the mechanisms by which insulin and IGF-1 receptors exert different effects on gene expression...
  34. ncbi Tissue-specific insulin resistance in type 2 diabetes: lessons from gene-targeted mice
    J Nakae
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Ann Med 33:22-7. 2001
    ..Here we review recent progress in the field and assess its relevance to the pathogenesis of diabetes in humans...
  35. pmc Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance
    Haruka Okamoto
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 116:775-82. 2006
    ..We propose that beta cell compensation to insulin resistance is a proliferative response of existing beta cells to growth factor signaling and requires FoxO1 nuclear exclusion...
  36. ncbi Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic beta-cell mass
    Jean Buteau
    Department of Medicine, Naomi Berrie Diabetes Center, Columbia University Medical Center, Berrie Research Pavilion, 1150 St Nicholas Ave, Room 238, New York, NY 10032, USA
    Diabetes 55:1190-6. 2006
    ..We propose that FoxO1 mediates the pleiotropic effects of the glucoincretin hormone on cell proliferation and survival...
  37. pmc Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism
    Michihiro Matsumoto
    Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA
    J Clin Invest 116:2464-72. 2006
    ....
  38. pmc SirT1 gain of function increases energy efficiency and prevents diabetes in mice
    Alexander S Banks
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 8:333-41. 2008
    ..These findings have important implications for Sirtuin-based therapies in humans...
  39. pmc n-3 Fatty acids decrease arterial low-density lipoprotein cholesterol delivery and lipoprotein lipase levels in insulin-resistant mice
    Chuchun L Chang
    Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Arterioscler Thromb Vasc Biol 30:2510-7. 2010
    ..To determine whether n-3 fatty acids (n-3) influence arterial cholesterol delivery and lipoprotein lipase (LpL) levels in insulin-resistant mice...
  40. pmc The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth
    Tadahiro Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 110:1839-47. 2002
    ..We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts...
  41. pmc Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action
    Haruka Okamoto
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Clin Invest 115:1314-22. 2005
    ..Conversely, the rate of glucose production was increased approximately 2-fold in L1 mice. Thus, restoration of hepatic insulin signaling in Insr knockout mice fails to normalize the in vivo response to insulin...
  42. ncbi Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver
    Michihiro Matsumoto
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell Metab 6:208-16. 2007
    ..The data provide a unifying mechanism for regulation of hepatic glucose production by cAMP and insulin...
  43. pmc A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
    Tadahiro Kitamura
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    J Clin Invest 117:2477-85. 2007
    ..Notch/Foxo1 cooperation may integrate environmental cues through Notch with metabolic cues through Foxo1 to regulate progenitor cell maintenance and differentiation...
  44. ncbi The forkhead transcription factor Foxo1 regulates adipocyte differentiation
    Jun Nakae
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Dev Cell 4:119-29. 2003
    ..We propose that Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes adipocyte differentiation...
  45. pmc The effect of insulin signaling on female reproductive function independent of adiposity and hyperglycemia
    Anindita Nandi
    Columbia University Medical Center, Russ Berrie Medical Pavilion, Room 608, 1150 St Nicholas Avenue, New York, New York 10032, USA
    Endocrinology 151:1863-71. 2010
    ..Thus, abnormal insulin signaling, independent of adipose tissue mass, adipokine expression levels, and hyperglycemia, can affect parameters of the female hypothalamic-pituitary-gonadal axis and pregnancy outcomes...
  46. pmc Hepatic FoxO1 ablation exacerbates lipid abnormalities during hyperglycemia
    Rebecca A Haeusler
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 285:26861-8. 2010
    ....
  47. ncbi Effects of insulin on prenylation as a mechanism of potentially detrimental influence of hyperinsulinemia
    B Draznin
    Denver Veterans Affairs Medical Center, Department of Medicine, University of Colorado Health Sciences Center, 80220, USA
    Endocrinology 141:1310-6. 2000
    ..This aspect of insulin action may represent one facet of the molecular mechanism of the potentially detrimental influence of hyperinsulinemia...
  48. ncbi Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance
    Hengjiang Dong
    Department of Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York, USA
    Diabetes 54:367-72. 2005
    ..These in vivo data support the concept, therefore, that PC-1 plays a role in insulin resistance and suggest that animals with overexpression of human PC-1 in liver may be interesting models to investigate this pathological process...
  49. ncbi Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes
    David Frescas
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032
    J Biol Chem 280:20589-95. 2005
    ..Selective modulation of the FoxO/Sirtuin interaction represents a promising therapeutic modality for metabolic disorders...
  50. pmc Hepatic insulin signaling regulates VLDL secretion and atherogenesis in mice
    Seongah Han
    Division of Molecular Medicine, Department of Medicine, Columbia University, 630 West 168th St, New York, New York 10032, USA
    J Clin Invest 119:1029-41. 2009
    ..These findings suggest a dual action of hepatic IR on lipoprotein levels, in which the ability to increase VLDL apoB and lipid secretion via AKT/GSK is offset by upregulation of Ldlr...
  51. ncbi Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice
    Jennifer Altomonte
    Carl C Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Am J Physiol Endocrinol Metab 285:E718-28. 2003
    ..These results demonstrated that functional inhibition of Foxo1, caused by hepatic expression of its mutant, is associated with reduced hepatic gluconeogenic activity and improved fasting glycemia in diabetic mice...
  52. pmc The impact of macrophage insulin resistance on advanced atherosclerotic plaque progression
    Ira Tabas
    Department of Medicine, Columbia University, 630 West 168th St, New York, NY 10032, USA
    Circ Res 106:58-67. 2010
    ..These processes may therefore provide an important mechanistic link among insulin resistance, plaque necrosis, and atherothrombotic vascular disease and suggest novel therapeutic approaches to this expanding health problem...
  53. ncbi Insulin receptor knockout mice
    Tadahiro Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Annu Rev Physiol 65:313-32. 2003
    ....
  54. pmc Increased CD36 protein as a response to defective insulin signaling in macrophages
    Chien Ping Liang
    Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York 10032, USA
    J Clin Invest 113:764-73. 2004
    ..The results suggest that defective macrophage insulin signaling predisposes to foam cell formation and atherosclerosis in insulin-resistant states and that this is reversed in vivo by treatment with PPAR-gamma activators...
  55. ncbi Proinsulin in girls: relationship to obesity, hyperinsulinemia, and puberty
    Daisy Chin
    Department of Pediatrics, Division of Pediatric Endocrinology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Endocrinol Metab 87:4673-7. 2002
    ..In fact, the lower fasting PI/I of the highest HOMA-IR quartile vs. the lowest HOMA quartile indicates more efficient conversion of PI to I in the presence of increasing IR in these girls...
  56. ncbi Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake
    Tadahiro Kitamura
    Department of Medicine, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA
    Nat Med 12:534-40. 2006
    ..Thus, FoxO1 represents a shared component of pathways integrating food intake and peripheral metabolism...
  57. ncbi Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions
    Seongah Han
    Department of Medicine, Columbia University, New York, New York 10032, USA
    Cell Metab 3:257-66. 2006
    ..These studies suggest that defective insulin signaling and reduced Akt activity impair the ability of macrophages to deal with ER stress-induced apoptosis within atherosclerotic plaques...
  58. pmc Mechanisms of disease: using genetically altered mice to study concepts of type 2 diabetes
    Derek LeRoith
    Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L Levy Place, Atran AB4 36, Box 1055, New York, NY 10029 6574, USA
    Nat Clin Pract Endocrinol Metab 4:164-72. 2008
    ....
  59. pmc The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake
    Leona Plum
    Naomi Berrie Diabetes Center and Department of Medicine, Columbia University, New York, New York, USA
    Nat Med 15:1195-201. 2009
    ..The dissociation of food intake from energy expenditure in Pomc-Foxo1(-/-) mice represents a model for therapeutic intervention in obesity and raises the possibility of targeting Cpe to develop weight loss medications...
  60. pmc Uncoupling of acetylation from phosphorylation regulates FoxO1 function independent of its subcellular localization
    Li Qiang
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 285:27396-401. 2010
    ..It can be envisaged that FoxO1 exists in multiple nuclear forms with distinct activities depending on the balance of acetylation and phosphorylation...
  61. pmc The double life of Irs
    Rebecca A Haeusler
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10027, USA
    Cell Metab 8:7-9. 2008
    ..Two studies in this issue (Kubota et al., 2008; Dong et al., 2008) on the insulin-signaling adaptors Irs1 and Irs2 prompt a critical reappraisal of the physiology of fasting and of the integrated control of hepatic insulin action...
  62. pmc Regulation of pancreatic juxtaductal endocrine cell formation by FoxO1
    Tadahiro Kitamura
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 100321, USA
    Mol Cell Biol 29:4417-30. 2009
    ..We conclude that FoxO1+ Ins(-) juxtaductal cells represent a hitherto-unrecognized pancreatic cell population with in vitro capability of endocrine differentiation...
  63. ncbi Mouse models of insulin resistance
    Anindita Nandi
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Physiol Rev 84:623-47. 2004
    ..Moreover, experimental crosses among mutant mice have shed light onto the polygenic nature of the interactions underlying this complex metabolic condition...
  64. ncbi New insights into the integrated physiology of insulin action
    Yukari Kitamura
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Rev Endocr Metab Disord 5:143-9. 2004
  65. ncbi Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development
    A Louvi
    Department of Genetics and Development, Columbia University, New York, New York, 10032, USA
    Dev Biol 189:33-48. 1997
    ..Therefore, these results provide genetic evidence that the growth-promoting function of IGF-II during mouse embryogenesis is mediated in part by signaling through the insulin receptor...
  66. ncbi Signalling through IGF-I and insulin receptors: where is the specificity?
    Jane J Kim
    Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Growth Horm IGF Res 12:84-90. 2002
    ....
  67. ncbi Mouse models of insulin resistance
    Marta Letizia Hribal
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Am J Physiol Endocrinol Metab 282:E977-81. 2002
    ..We review recent progress and try to reconcile areas of apparent controversy surrounding insulin signaling in skeletal muscle and pancreatic beta-cells...
  68. pmc Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor
    Shouhong Xuan
    Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Clin Invest 110:1011-9. 2002
    ..These observations reveal a requirement of IGF1R-mediated signaling for insulin secretion...
  69. ncbi All roads lead to FoxO
    Michihiro Matsumoto
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cell Metab 1:215-6. 2005
    ..2005; Wang et al., 2005). The findings provide yet another mechanism by which metabolic and stress responses are integrated via phosphorylation of FoxO proteins...
  70. pmc The impact of insulin resistance on macrophage death pathways in advanced atherosclerosis
    Ira Tabas
    Department of Medicine, 630 West 168th Street, Columbia University, New York, NY 10032, USA
    Novartis Found Symp 286:99-109; discussion 109-12, 162-3, 196-203. 2007
    ....
  71. pmc Notch alters VEGF responsiveness in human and murine endothelial cells by direct regulation of VEGFR-3 expression
    Carrie J Shawber
    Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York 10032, USA
    J Clin Invest 117:3369-82. 2007
    ..These results demonstrate that Notch1 and VEGFR-3 interact genetically, that Notch directly induces VEGFR-3 in blood endothelial cells to regulate vascular development, and that Notch may function in tumor lymphangiogenesis...
  72. pmc Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes
    Franck Mauvais-Jarvis
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 109:141-9. 2002
    ..Furthermore, Pik3r1 heterozygosity protects mice with genetic insulin resistance from developing diabetes. These data suggest that regulation of p85alpha levels may provide a novel therapeutic target for the treatment of type 2 diabetes...
  73. ncbi The tangled path to glucose production
    Michihiro Matsumoto
    Nat Med 12:33-4; discussion 34. 2006
  74. ncbi Overexpression of the insulin receptor inhibitor PC-1/ENPP1 induces insulin resistance and hyperglycemia
    Betty A Maddux
    Department of Medicine and Diabetes Center, University of California, San Francisco 94143 1616, USA
    Am J Physiol Endocrinol Metab 290:E746-9. 2006
    ....
  75. pmc Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF-alpha
    Massimo Federici
    Center for Atherosclerosis, Policlinico Tor Vergata University Hospital, Rome, Italy
    J Clin Invest 115:3494-505. 2005
    ..Our results suggest that an interplay between reduced insulin action and unchecked TACE activity promotes diabetes and vascular inflammation...
  76. ncbi Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity
    Atsushi Tsuchida
    Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113 8655, Japan
    J Biol Chem 279:30817-22. 2004
    ....
  77. ncbi Analysis of compensatory beta-cell response in mice with combined mutations of Insr and Irs2
    Jane J Kim
    Deparment of Pediatrics, University of California, San Diego, California, USA
    Am J Physiol Endocrinol Metab 292:E1694-701. 2007
    ..The eventual failure of compensatory insulin secretion suggests that a comprehensive treatment of beta-cell dysfunction in type 2 diabetes should positively affect both aspects of beta-cell physiology...
  78. ncbi Nuclear forkhead box O1 controls and integrates key signaling pathways in hepatocytes
    Mourad Naimi
    Institut National de la Santé et de la Recherche Médicale U145, Institut Federatif de Recherche 50, Faculte de Medecine, Avenue de Valombrose, F 06107 Nice, France
    Endocrinology 148:2424-34. 2007
    ..We propose that Foxo1 turns on a feed-forward loop, relayed by p38 and acting to amplify both PKB activation and Foxo1 inhibition. To conclude, key signaling pathways are activated in hepatocytes through nuclear Foxo1...
  79. ncbi Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction
    Pere Puigserver
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 423:550-5. 2003
    ..We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis...
  80. ncbi Testis determination requires insulin receptor family function in mice
    Serge Nef
    Center for Developmental Biology, University of Texas, Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390 9133, USA
    Nature 426:291-5. 2003
    ..Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination...
  81. pmc The role of membrane glycoprotein plasma cell antigen 1/ectonucleotide pyrophosphatase phosphodiesterase 1 in the pathogenesis of insulin resistance and related abnormalities
    Ira D Goldfine
    Department of Medicine and Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
    Endocr Rev 29:62-75. 2008
    ..These data suggest therefore that PC-1 is a candidate protein that may play a role in human insulin resistance and T2D by its overexpression, its overactivity, or both...
  82. ncbi Turning up the heat in the fat cell
    Domenico Accili
    Nat Med 10:1168-9. 2004
  83. ncbi A note of caution on the Knockout Mouse Project
    Domenico Accili
    Nat Genet 36:1132. 2004

Research Grants32

  1. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2010
    ..Therefore, it is hoped that by identifying mechanisms of action and interacting partners, new ways to modulate its function can be found. ..
  2. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2010
    ..The driving theme of the proposed work is to define cellular pathways that can be enlisted in the clinic against cell dysfunction. ..
  3. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2005
    ..The upshot of these investigations is that manipulation of Foxo1 function in endocrine precursor cells may become an adjuvant therapy in the treatment of diabetes. ..
  4. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2006
    ..Therefore, it is hoped that by identifying mechanisms of action and interacting partners, new ways to modulate its function can be found. ..
  5. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2007
    ..Therefore, it is hoped that by identifying mechanisms of action and interacting partners, new ways to modulate its function can be found. ..
  6. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2007
    ..abstract_text> ..
  7. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2009
    ..Therefore, it is hoped that by identifying mechanisms of action and interacting partners, new ways to modulate its function can be found. ..
  8. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2009
    ..abstract_text> ..
  9. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2005
    ..These investigations will shed new light onto the mechanisms by which insulin resistance causes hyperglycemia, and disclose new approaches to the treatment of diabetes. ..
  10. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2003
    ..These investigations will shed new light onto the mechanisms by which insulin resistance causes hyperglycemia, and disclose new approaches to the treatment of diabetes. ..
  11. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2002
    ..Additional mapping of the QTLs is proposed as a preliminary to positional cloning of the relevant genes. ..
  12. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2003
    ..These investigations will shed new light onto the mechanisms by which insulin resistance causes hyperglycemia, and disclose new approaches to the treatment of diabetes. ..
  13. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2003
    ..Additional mapping of the QTLs is proposed as a preliminary to positional cloning of the relevant genes. ..
  14. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2009
    ..The driving theme of the proposed work is to define cellular pathways that can be enlisted in the clinic against cell dysfunction. ..
  15. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2002
    ..These investigations will shed new light onto the mechanisms by which insulin resistance causes hyperglycemia, and disclose new approaches to the treatment of diabetes. ..
  16. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2001
    ..Additional mapping of the QTLs is proposed as a preliminary to positional cloning of the relevant genes. ..
  17. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2004
    ..Additional mapping of the QTLs is proposed as a preliminary to positional cloning of the relevant genes. ..
  18. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2004
    ..The upshot of these investigations is that manipulation of Foxo1 function in endocrine precursor cells may become an adjuvant therapy in the treatment of diabetes. ..
  19. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2004
    ..These investigations will shed new light onto the mechanisms by which insulin resistance causes hyperglycemia, and disclose new approaches to the treatment of diabetes. ..
  20. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2004
    ..The upshot of these investigations is that manipulation of Foxo1 function in endocrine precursor cells may become an adjuvant therapy in the treatment of diabetes. ..
  21. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2005
    ..abstract_text> ..
  22. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2006
    ..The upshot of these investigations is that manipulation of Foxo1 function in endocrine precursor cells may become an adjuvant therapy in the treatment of diabetes. ..
  23. MOUSE MODELS OF INSULIN RESISTANCE
    Domenico Accili; Fiscal Year: 2006
    ..abstract_text> ..
  24. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2003
    ..The upshot of these investigations is that manipulation of Foxo1 function in endocrine precursor cells may become an adjuvant therapy in the treatment of diabetes. ..
  25. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2007
    ..The upshot of these investigations is that manipulation of Foxo1 function in endocrine precursor cells may become an adjuvant therapy in the treatment of diabetes. ..
  26. ROLE OF FORKHEAD PROTEINS IN INSULIN ACTION
    Domenico Accili; Fiscal Year: 2001
    ..These investigations will shed new light onto the mechanisms by which insulin resistance causes hyperglycemia, and disclose new approaches to the treatment of diabetes. ..