P Newsholme

Summary

Affiliation: University College Dublin
Country: Ireland

Publications

  1. doi request reprint Mitochondria and diabetes. An intriguing pathogenetic role
    Philip Newsholme
    UCD School of Biomolecular and Biomedical Science, Belfield, Dublin 4, Ireland
    Adv Exp Med Biol 942:235-47. 2012
  2. pmc A proteomic analysis of the functional effects of fatty acids in NIH 3T3 fibroblasts
    Juliana Magdalon
    Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
    Lipids Health Dis 10:218. 2011
  3. ncbi request reprint New insights into amino acid metabolism, beta-cell function and diabetes
    Philip Newsholme
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 108:185-94. 2005
  4. pmc Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity
    P Newsholme
    School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    J Physiol 583:9-24. 2007
  5. ncbi request reprint Amino acid metabolism, insulin secretion and diabetes
    P Newsholme
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    Biochem Soc Trans 35:1180-6. 2007
  6. ncbi request reprint Glutamine and glutamate--their central role in cell metabolism and function
    Philip Newsholme
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
    Cell Biochem Funct 21:1-9. 2003
  7. doi request reprint Nutrient regulation of insulin secretion and beta-cell functional integrity
    Philip Newsholme
    School of Biomolecular and Biomedical Sciences, Conway Institute, UCD Dublin, Belfield, Dublin 4, Ireland
    Adv Exp Med Biol 654:91-114. 2010
  8. doi request reprint Insights into the critical role of NADPH oxidase(s) in the normal and dysregulated pancreatic beta cell
    P Newsholme
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute and Health Sciences Centre, UCD Dublin, Belfield, Dublin 4, Ireland
    Diabetologia 52:2489-98. 2009
  9. doi request reprint Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide
    Philip Newsholme
    School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 118:341-9. 2010
  10. ncbi request reprint Life and death decisions of the pancreatic beta-cell: the role of fatty acids
    Philip Newsholme
    School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland
    Clin Sci (Lond) 112:27-42. 2007

Collaborators

Detail Information

Publications43

  1. doi request reprint Mitochondria and diabetes. An intriguing pathogenetic role
    Philip Newsholme
    UCD School of Biomolecular and Biomedical Science, Belfield, Dublin 4, Ireland
    Adv Exp Med Biol 942:235-47. 2012
    ..We will review the molecular basis for optimal mitochondrial function or mechanisms of dysfunction and correlate with pathology of identified diseases and aging...
  2. pmc A proteomic analysis of the functional effects of fatty acids in NIH 3T3 fibroblasts
    Juliana Magdalon
    Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
    Lipids Health Dis 10:218. 2011
    ..However, modulation of α-enolase and FBP-1 expression by fatty acids was not validated by the Western blot technique...
  3. ncbi request reprint New insights into amino acid metabolism, beta-cell function and diabetes
    Philip Newsholme
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 108:185-94. 2005
    ..Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion...
  4. pmc Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity
    P Newsholme
    School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    J Physiol 583:9-24. 2007
    ..Thus NADPH oxidase may be a useful target for intervention strategies based on reversing the negative impact of glucolipotoxicity in diabetes...
  5. ncbi request reprint Amino acid metabolism, insulin secretion and diabetes
    P Newsholme
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    Biochem Soc Trans 35:1180-6. 2007
    ..Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion...
  6. ncbi request reprint Glutamine and glutamate--their central role in cell metabolism and function
    Philip Newsholme
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
    Cell Biochem Funct 21:1-9. 2003
    ..In this review we highlight the specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells and in each case relate key aspects of metabolism to cell function...
  7. doi request reprint Nutrient regulation of insulin secretion and beta-cell functional integrity
    Philip Newsholme
    School of Biomolecular and Biomedical Sciences, Conway Institute, UCD Dublin, Belfield, Dublin 4, Ireland
    Adv Exp Med Biol 654:91-114. 2010
    ..Primary MCFs in the beta-cell include ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol and are discussed in detail in this article...
  8. doi request reprint Insights into the critical role of NADPH oxidase(s) in the normal and dysregulated pancreatic beta cell
    P Newsholme
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute and Health Sciences Centre, UCD Dublin, Belfield, Dublin 4, Ireland
    Diabetologia 52:2489-98. 2009
    ..The various beta cell isoforms of NADPH oxidase (described in this review) may, via differences in the kinetics and species of ROS generated, positively and negatively regulate insulin secretion and cell survival...
  9. doi request reprint Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide
    Philip Newsholme
    School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 118:341-9. 2010
    ..NO* synthesis will be increased during exercise in the vascular endothelial cells so promoting blood flow. We suggest that exercise may promote improvements in health due to positive metabolic and cytokine-mediated effects...
  10. ncbi request reprint Life and death decisions of the pancreatic beta-cell: the role of fatty acids
    Philip Newsholme
    School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland
    Clin Sci (Lond) 112:27-42. 2007
    ..In this review, we describe the effects of exogenous and endogenous fatty acids on beta-cell metabolism and gene and protein expression, and have explored the outcomes with respect to insulin secretion and beta-cell integrity...
  11. ncbi request reprint Amino acids and diabetes: implications for endocrine, metabolic and immune function
    Philip Newsholme
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute and UCD Institute for Sport and Health, UCD Dublin, Belield, Dublin 4, Ireland
    Front Biosci (Landmark Ed) 16:315-39. 2011
    ....
  12. ncbi request reprint Identification of a novel complement-dependent serum-elicited inward current in the Xenopus oocyte provoking Ca2+ influx and subsequent activation of Cl- channels
    P Newsholme
    Department of Biochemistry, University College Dublin, Ireland
    Biochem Pharmacol 57:491-501. 1999
    ..As overactivation of complement does play a role in many inflammatory or autoimmune diseases, inhibition of early complement-mediated ion flux might restrict tissue damage and aid recovery from such diseases...
  13. ncbi request reprint Importance of glutamine metabolism in murine macrophages and human monocytes to L-arginine biosynthesis and rates of nitrite or urea production
    C Murphy
    Department of Biochemistry, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 95:397-407. 1998
    ..Additionally, the rate of L-arginine biosynthesis from glutamine may be increased on immunostimulation of the macrophage...
  14. ncbi request reprint A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine
    G Dixon
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    J Endocrinol 179:447-54. 2003
    ..The metabolism ofL -alanine in the beta-cell may result in stimulation of insulin secretion via generation of metabolic stimulus secretion coupling factors such asL -glutamate...
  15. ncbi request reprint The importance of redox shuttles to pancreatic beta-cell energy metabolism and function
    K Bender
    UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    Biochem Soc Trans 34:811-4. 2006
    ..This work may provide evidence for a central role of Aralar1 in the regulation of nutrient metabolism in the beta-cells...
  16. ncbi request reprint 13C NMR analysis reveals a link between L-glutamine metabolism, D-glucose metabolism and gamma-glutamyl cycle activity in a clonal pancreatic beta-cell line
    L Brennan
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Diabetologia 46:1512-21. 2003
    ..D-glucose, under appropriate conditions, can be converted to L-glutamate via an aminotransferase catalysed step...
  17. ncbi request reprint A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of L-alanine is important to the regulation of insulin secretion
    Lorraine Brennan
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
    Diabetes 51:1714-21. 2002
    ..Thus L-alanine metabolism, in addition to the enhancing effect on glucose metabolism, contributes to the stimulatory effects of this amino acid on insulin secretion in vitro...
  18. ncbi request reprint Glutamine and glutamate as vital metabolites
    P Newsholme
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College of Dublin, Belfield, Dublin, Ireland
    Braz J Med Biol Res 36:153-63. 2003
    ..Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function...
  19. ncbi request reprint Macrophage-mediated lysis of a beta-cell line, tumour necrosis factor-alpha release from bacillus Calmette-Guérin (BCG)-activated murine macrophages and interleukin-8 release from human monocytes are dependent on extracellular glutamine concentration and
    C Murphy
    Department of Biochemistry, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 96:89-97. 1999
    ..Thus glutamine metabolism may be essential for generation of cytotoxic products from macrophages, including tumour necrosis factor-alpha...
  20. ncbi request reprint Investigation of the effects of sulfonylurea exposure on pancreatic beta cell metabolism
    Lorraine Brennan
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Ireland
    FEBS J 273:5160-8. 2006
    ....
  21. doi request reprint Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids
    P Newsholme
    School of Biomedical Sciences, Curtin University, PO Box U1987, Perth, Western Australia 6845, Australia
    J Endocrinol 214:11-20. 2012
    ....
  22. ncbi request reprint Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection?
    P Newsholme
    Department of Biochemistry, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    J Nutr 131:2515S-22S; discussion 2523S-4S. 2001
    ..Evidence to support the hypothesis that glutamine is beneficially immunomodulatory in animal models of infection and trauma, as well as trauma in humans, is provided...
  23. ncbi request reprint Evidence for a sustained increase in clonal beta-cell basal intracellular Ca2+ levels after incubation in the presence of newly diagnosed Type-1 diabetic patient sera. Possible role in serum-induced inhibition of insulin secretion
    S J Conroy
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    J Endocrinol 173:53-62. 2002
    ....
  24. ncbi request reprint Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene, and protein expression in a clonal pancreatic beta-cell line
    Mary Corless
    School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    J Endocrinol 190:719-27. 2006
    ..These observations indicate important long-term effects of l-glutamine in regulating beta-cell gene expression, signaling, and secretory function...
  25. pmc Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes
    Seth L Masters
    Immunology Research Centre, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland
    Nat Immunol 11:897-904. 2010
    ..Our findings identify previously unknown mechanisms in the pathogenesis of type 2 diabetes and treatment of pathology caused by IAPP...
  26. ncbi request reprint L-Alanine induces changes in metabolic and signal transduction gene expression in a clonal rat pancreatic beta-cell line and protects from pro-inflammatory cytokine-induced apoptosis
    Grainne A Cunningham
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 109:447-55. 2005
    ..Specific amino acids may therefore play a key role in beta-cell function in vivo...
  27. ncbi request reprint Pro-inflammatory cytokines increase glucose, alanine and triacylglycerol utilization but inhibit insulin secretion in a clonal pancreatic beta-cell line
    Aoife Kiely
    School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    J Endocrinol 195:113-23. 2007
    ....
  28. ncbi request reprint Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity
    Gordon Dixon
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 106:191-9. 2004
    ..This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the beta-cell...
  29. pmc Overexpression of the malate-aspartate NADH shuttle member Aralar1 in the clonal beta-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism
    Katrin Bender
    UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute, UCD Dublin, Dublin 4, Ireland
    Clin Sci (Lond) 117:321-30. 2009
    ..We conclude that Aralar1 is a key metabolic control site in insulin-secreting cells...
  30. doi request reprint Toll-like receptor agonist induced changes in clonal rat BRIN-BD11 beta-cell insulin secretion and signal transduction
    Aoife Kiely
    School of Biomolecular and Biomedical Sciences, Conway Institute and Health Sciences Centre, UCD Dublin, Belfield, Dublin 4, Ireland
    J Endocrinol 202:365-73. 2009
    ..Further incubation for 24 h in the absence of LPS resulted in the recovery of chronic insulin secretion. The negative beta-cell effects of LPS may contribute to hyperglycaemia in vivo...
  31. doi request reprint Saturated and unsaturated (including arachidonic acid) non-esterified fatty acid modulation of insulin secretion from pancreatic beta-cells
    Deirdre Keane
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, UCD Dublin, Belfield, Dublin 4, Ireland
    Biochem Soc Trans 36:955-8. 2008
    ....
  32. ncbi request reprint Glucose, but not glutamine, protects against spontaneous and anti-Fas antibody-induced apoptosis in human neutrophils
    Declan A Healy
    Department of Biochemistry, University College Dublin, Belfield, Dublin 4, Ireland
    Clin Sci (Lond) 103:179-89. 2002
    ..5 mM glucose. The protective effect of glucose against apoptosis may be mediated by maintenance of the intracellular ATP concentration...
  33. ncbi request reprint Glutamine, gene expression, and cell function
    Rui Curi
    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brasil
    Front Biosci 12:344-57. 2007
    ..In this review, we have attempted to identify some of the common mechanisms underlying glutamine dependent changes in gene and protein expression and cellular function...
  34. ncbi request reprint Mitochondria-derived glutamate at the interplay between branched-chain amino acid and glucose-induced insulin secretion
    Christophe Broca
    DBC 9100, Department of Internal Medicine, University Medical Centre, 1 rue Michel Servet, CH 1211 Geneva 4, Switzerland
    FEBS Lett 545:167-72. 2003
    ..This study demonstrates that glucose stimulates glutamate generation, whereas branched-chain amino acids promote competitive glutamate expenditure...
  35. ncbi request reprint Glucose metabolism in lymphoid and inflammatory cells and tissues
    Philip C Calder
    Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton, UK
    Curr Opin Clin Nutr Metab Care 10:531-40. 2007
    ..To examine the role of glucose as a fuel for immune cells and the influence of glucose supply on immune-cell functional responses...
  36. ncbi request reprint Comparative toxicity of oleic and linoleic acid on human lymphocytes
    Maria F Cury-Boaventura
    Department of Physiology and Biophysics, Institute of Biomedical Sciences, Av Prof Lineu Prestes, 1524, CEP 05508 900, University of Sao Paulo, SP, Brazil
    Life Sci 78:1448-56. 2006
    ..OA may offer an immunological less problematic alternative to LA with respect to fatty acid composition of parenteral nutritional emulsions...
  37. ncbi request reprint New insights into fatty acid modulation of pancreatic beta-cell function
    Esther P Haber
    Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Int Rev Cytol 248:1-41. 2006
    ..Lipids can be transferred from leukocytes (macrophages) to pancreatic islets in coculture. This latter process may provide an additional source of FAs that may play a significant role in the regulation of insulin secretion...
  38. ncbi request reprint Genes regulated by arachidonic and oleic acids in Raji cells
    Rozangela Verlengia
    Methodist University of Piracicaba, Faculty of Sciences of Health, Physical Education, Sao Paulo, Brazil
    Lipids 38:1157-65. 2003
    ..These results led us to conclude that the effect of these FA on B-lymphocytes includes regulation of gene expression. Thus, diets enriched with fat containing OA or AA may affect B lymphocyte function in vivo...
  39. ncbi request reprint Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst in human neutrophils by adrenaline: inhibition of Phospholipase A2 activity but not p47phox phosphorylation and translocation
    Yvonne M O'Dowd
    Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, 4, Dublin, Ireland
    Biochem Pharmacol 67:183-90. 2004
    ..We suggest that adrenaline inhibits fMLP induced superoxide production upstream of the NADPH oxidase via a mechanism involving PKA and cPLA(2)...
  40. doi request reprint In vivo and in vitro studies of GAD-antibody positive subjects with Type 2 diabetes: A distinct sub-phenotype
    Donal J O'Gorman
    Metabolic Research Unit, Department of Endocrinology, St James s Hospital, Trinity College Dublin, Dublin 8, Ireland
    Diabetes Res Clin Pract 80:365-70. 2008
    ..TCC formation may be partly responsible for the insulin secretory dysfunction associated with this specific sub-type of Type 2 diabetes...
  41. ncbi request reprint Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function
    Renata Gorjao
    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av Prof Lineu Prestes, 1524, 05508 900, Butanta, Sao Paulo, SP, Brazil
    Clin Nutr 25:923-38. 2006
    ..The effect of a docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on human leukocyte function was investigated...
  42. ncbi request reprint Glutamine delays spontaneous apoptosis in neutrophils
    Tania C Pithon-Curi
    Methodist University of Piracicaba, FACEF, Sao Paulo, SP, Brazil
    Am J Physiol Cell Physiol 284:C1355-61. 2003
    ..Therefore, glutamine protects from events associated with triggering and executing apoptosis in both rat and human neutrophils...
  43. ncbi request reprint Effects of EPA and DHA on proliferation, cytokine production, and gene expression in Raji cells
    Rozangela Verlengia
    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
    Lipids 39:857-64. 2004
    ..However, remarkable differences were observed between DHA and EPA, demonstrating that specific effects of these FA may be responsible for the marked differences in edible oil effects on immune function in vivo reported by others...