D J Drucker

Summary

Affiliation: University of Toronto
Country: Canada

Publications

  1. ncbi Extrahypothalamic expression of the glucagon-like peptide-2 receptor is coupled to reduction of glutamate-induced cell death in cultured hippocampal cells
    J A Lovshin
    Department of Medicine, University of Toronto, Toronto General Hospital, Banting and Best Diabetes Center, Canada
    Endocrinology 145:3495-506. 2004
  2. pmc Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice
    Meghan Sauvé
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Diabetes 59:1063-73. 2010
  3. pmc Glucagon-like peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice
    Jacqueline A Koehler
    Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada
    Diabetes 58:2148-61. 2009
  4. pmc GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice
    Mohammad Hossein Noyan-Ashraf
    Toronto General Hospital, Toronto, Ontario, Canada
    Diabetes 58:975-83. 2009
  5. doi Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2
    Daniel J Drucker
    Department of Medicine, Mount Sinai Hospital, Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X5 email
    Annu Rev Physiol 76:561-83. 2014
  6. doi GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE(-/-) mice
    Naim Panjwani
    Departments of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto Ontario Canada M5G 1X5
    Endocrinology 154:127-39. 2013
  7. pmc Activation of enteroendocrine membrane progesterone receptors promotes incretin secretion and improves glucose tolerance in mice
    Grace B Flock
    Department of Medicine, Institute of Medical Sciences, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada
    Diabetes 62:283-90. 2013
  8. pmc Intestinotrophic glucagon-like peptide-2 (GLP-2) activates intestinal gene expression and growth factor-dependent pathways independent of the vasoactive intestinal peptide gene in mice
    Bernardo Yusta
    Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1X5
    Endocrinology 153:2623-32. 2012
  9. pmc Cardiovascular biology of the incretin system
    John R Ussher
    Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada
    Endocr Rev 33:187-215. 2012
  10. pmc Disruption of the murine Glp2r impairs Paneth cell function and increases susceptibility to small bowel enteritis
    Seung Jun Lee
    Department of Medicine, Mt Sinai Hospital, Samuel Lunenfeld Research Institute, 600 University Avenue, TCP5 1004, Toronto, Ontario, Canada
    Endocrinology 153:1141-51. 2012

Collaborators

Detail Information

Publications127 found, 100 shown here

  1. ncbi Extrahypothalamic expression of the glucagon-like peptide-2 receptor is coupled to reduction of glutamate-induced cell death in cultured hippocampal cells
    J A Lovshin
    Department of Medicine, University of Toronto, Toronto General Hospital, Banting and Best Diabetes Center, Canada
    Endocrinology 145:3495-506. 2004
    ..These findings establish the presence of a functional GLP-2-GLP-2R axis in the developing rodent brain and demonstrate that GLP-2 exerts cytoprotective actions in cells derived from the central nervous system...
  2. pmc Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice
    Meghan Sauvé
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Diabetes 59:1063-73. 2010
    ..We examined whether chemical inhibition or genetic elimination of DPP-4 activity affects cardiovascular function in normoglycemic and diabetic mice after experimental myocardial infarction...
  3. pmc Glucagon-like peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice
    Jacqueline A Koehler
    Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada
    Diabetes 58:2148-61. 2009
    ..Clinical reports link use of the glucagon-like peptide-1 receptor (GLP-1R) agonists exenatide and liraglutide to pancreatitis. However, whether these agents act on the exocrine pancreas is poorly understood...
  4. pmc GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice
    Mohammad Hossein Noyan-Ashraf
    Toronto General Hospital, Toronto, Ontario, Canada
    Diabetes 58:975-83. 2009
    ..However, the consequences of GLP-1R activation before ischemic myocardial injury remain unclear...
  5. doi Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2
    Daniel J Drucker
    Department of Medicine, Mount Sinai Hospital, Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X5 email
    Annu Rev Physiol 76:561-83. 2014
    ..Hence GLP-2 integrates nutrient-derived signals to optimize mucosal integrity and energy absorption. ..
  6. doi GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE(-/-) mice
    Naim Panjwani
    Departments of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto Ontario Canada M5G 1X5
    Endocrinology 154:127-39. 2013
    ....
  7. pmc Activation of enteroendocrine membrane progesterone receptors promotes incretin secretion and improves glucose tolerance in mice
    Grace B Flock
    Department of Medicine, Institute of Medical Sciences, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada
    Diabetes 62:283-90. 2013
    ..Intestine-restricted activation of membrane progesterone receptors may represent a novel approach for stimulation of incretin hormone secretion and control of glucose homeostasis...
  8. pmc Intestinotrophic glucagon-like peptide-2 (GLP-2) activates intestinal gene expression and growth factor-dependent pathways independent of the vasoactive intestinal peptide gene in mice
    Bernardo Yusta
    Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1X5
    Endocrinology 153:2623-32. 2012
    ....
  9. pmc Cardiovascular biology of the incretin system
    John R Ussher
    Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada
    Endocr Rev 33:187-215. 2012
    ....
  10. pmc Disruption of the murine Glp2r impairs Paneth cell function and increases susceptibility to small bowel enteritis
    Seung Jun Lee
    Department of Medicine, Mt Sinai Hospital, Samuel Lunenfeld Research Institute, 600 University Avenue, TCP5 1004, Toronto, Ontario, Canada
    Endocrinology 153:1141-51. 2012
    ..Although the Glp2r is dispensable for gut development and the response to colonic injury, Glp2r(-/-) mice exhibit enhanced sensitivity to small bowel injury, and abnormal host-bacterial interactions in the small bowel...
  11. ncbi Biological actions and therapeutic potential of the glucagon-like peptides
    Daniel J Drucker
    The Banting and Best Diabetes Centre, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
    Gastroenterology 122:531-44. 2002
    ..Hence, inhibitors of DP IV activity, or DP IV-resistant glucagon-like peptide analogues, may be alternative therapeutic approaches for treatment of human diseases...
  12. pmc Gut adaptation and the glucagon-like peptides
    D J Drucker
    The Banting and Best Diabetes Centre, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4
    Gut 50:428-35. 2002
    ..Hence GLP-2 may be therapeutically useful in diseases characterised by injury or dysfunction of the gastrointestinal epithelium...
  13. ncbi Development of glucagon-like peptide-1-based pharmaceuticals as therapeutic agents for the treatment of diabetes
    D J Drucker
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Canada
    Curr Pharm Des 7:1399-412. 2001
    ....
  14. doi The safety of incretin-based therapies--review of the scientific evidence
    Daniel J Drucker
    Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    J Clin Endocrinol Metab 96:2027-31. 2011
    ..Antidiabetic therapies based on potentiation of incretin action are now widely used; however, understanding of their long-term safety remains incomplete...
  15. ncbi Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo
    Laurie L Baggio
    Banting and Best Diabetes Centre, University of Toronto, Toronto General Hospital, 200 Elizabeth St, MBRW 4R 402, Toronto, Ontario Canada M5G 2C4
    Diabetes 53:S205-14. 2004
    ....
  16. ncbi Glucagon-like peptide-1 and the islet beta-cell: augmentation of cell proliferation and inhibition of apoptosis
    Daniel J Drucker
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4
    Endocrinology 144:5145-8. 2003
  17. pmc Gipr is essential for adrenocortical steroidogenesis; however, corticosterone deficiency does not mediate the favorable metabolic phenotype of Gipr(-/-) mice
    Holly E Bates
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Diabetes 61:40-8. 2012
    ....
  18. ncbi Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis
    Daniel J Drucker
    Department of Medicine, Toronto General Hospital, University Health Network, Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada M5G 2C4
    Mol Endocrinol 17:161-71. 2003
    ..Hence, peptide hormones, as exemplified by GLP-1 and GLP-2, may prove to be useful adjunctive tools for enhancement of cell differentiation, tissue regeneration, and cytoprotection for the treatment of human disease...
  19. ncbi Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes
    Daniel J Drucker
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, M5G 2C4, Canada
    Expert Opin Investig Drugs 12:87-100. 2003
    ....
  20. ncbi Enhancing incretin action for the treatment of type 2 diabetes
    Daniel J Drucker
    Department of Medicine, Toronto General Hospital, University of Toronto, Ontario, Canada
    Diabetes Care 26:2929-40. 2003
    ..To examine the mechanisms of action, therapeutic potential, and challenges inherent in the use of incretin peptides and dipeptidyl peptidase-IV (DPP-IV) inhibitors for the treatment of type 2 diabetes...
  21. ncbi Liraglutide
    Daniel J Drucker
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada
    Nat Rev Drug Discov 9:267-8. 2010
    ..In January 2010, liraglutide (Victoza; Novo Nordisk)--an injectable glucagon-like peptide 1 receptor agonist--was approved by the US FDA to improve glycaemic control in adults with type 2 diabetes mellitus...
  22. ncbi Glucagon-like peptide 2
    D J Drucker
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4
    J Clin Endocrinol Metab 86:1759-64. 2001
    ..The cytoprotective, reparative, and energy-retentive properties of GLP-2 suggests that GLP-2 may potentially be useful for the treatment of human disorders characterized by injury and/or dysfunction of the intestinal mucosal epithelium...
  23. ncbi Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action
    Daniel J Drucker
    Department of Medicine, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada
    Diabetes Care 30:1335-43. 2007
  24. ncbi Glucagon-like peptides
    D J Drucker
    Department of Medicine, The Toronto Hospital, Banting and Best Diabetes Centre, University of Toronto, Ontario, Canada
    Diabetes 47:159-69. 1998
    ..This review discusses recent advances in our understanding of the biological activity of the glucagon-like peptides...
  25. pmc The role of gut hormones in glucose homeostasis
    Daniel J Drucker
    Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
    J Clin Invest 117:24-32. 2007
    ..This article reviews the biological actions of gut hormones regulating glucose homeostasis, with an emphasis on mechanisms of action and the emerging therapeutic roles of gut hormones for the treatment of type 2 diabetes mellitus...
  26. ncbi Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV
    D J Drucker
    Department of Medicine, Toronto Hospital, University of Toronto, Ontario
    Nat Biotechnol 15:673-7. 1997
    ..Treatment of wild-type rats with r[Gly2]GLP-2 produced a statistically significant increase in small bowel mass. DPP-IV-mediated inactivation of GLP-2 is a critical determinant of the growth factor-like properties of GLP-2...
  27. ncbi The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes
    Daniel J Drucker
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Lancet 368:1696-705. 2006
    ..However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes...
  28. ncbi Biologic actions and therapeutic potential of the proglucagon-derived peptides
    Daniel J Drucker
    Banting and Best Diabetes Centre, Toronto, Ontario, Canada
    Nat Clin Pract Endocrinol Metab 1:22-31. 2005
    ..Thus the modulation of proglucagon-derived peptides has therapeutic potential for the treatment of diabetes and intestinal disease...
  29. ncbi New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2
    D J Drucker
    Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada M5G2C4
    Ann N Y Acad Sci 921:226-32. 2000
    ..The biological actions of the glucagon-like peptides suggest they may have therapeutic efficacy in diabetes (GLP-1) or intestinal disorders (GLP-2)...
  30. ncbi The biology of incretin hormones
    Daniel J Drucker
    Department of Medicine, The Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario M5G 2C4, Canada
    Cell Metab 3:153-65. 2006
    ..This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes...
  31. ncbi Minireview: the glucagon-like peptides
    D J Drucker
    Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario M5G 2C4 Canada
    Endocrinology 142:521-7. 2001
    ....
  32. pmc GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms
    Grace Flock
    Samuel Lunenfeld Research Institute Mt Sinai Hospital, 600 University Avenue TCP5 1004, Toronto, Ontario, Canada
    Endocrinology 152:374-83. 2011
    ..In contrast, AR231453 inhibits gastric emptying independent of incretin, Y2R, or Glp2 receptors through GPR119-dependent pathways. Hence, GPR119 engages multiple complementary pathways for control of glucose homeostasis...
  33. ncbi Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors
    Tanya Hansotia
    Banting and Best Diabetes Centre, Department of Medicine, Toronto General Hospital, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4
    Diabetes 53:1326-35. 2004
    ....
  34. ncbi The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription
    M Wang
    Banting and Best Diabetes Centre, Toronto Hospital, University of Toronto, Canada
    J Biol Chem 270:12646-52. 1995
    ..These data demonstrate that the LIM domain homeobox gene isl-1 1) is not constrained from DNA binding by its LIM domains and 2) functions as a positive regulator of proglucagon gene transcription in the endocrine pancreas...
  35. ncbi Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action
    L A Scrocchi
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada
    Diabetes 49:1552-60. 2000
    ....
  36. ncbi Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling
    J Lovshin
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, Toronto, Ontario M5G 2C4, Canada
    J Biol Chem 276:21489-99. 2001
    ..These findings illustrate that CNS GLP-2R expression is not restricted to hypothalamic nuclei and demonstrate that the anorectic effects of GLP-2 are transient and modulated by the presence or absence of GLP-1R signaling in vivo...
  37. ncbi Divergent tissue-specific and developmental expression of receptors for glucagon and glucagon-like peptide-1 in the mouse
    R V Campos
    Department of Medicine, University of Toronto, Ontario, Canada
    Endocrinology 134:2156-64. 1994
    ....
  38. ncbi The HeLa cell glucagon-like peptide-2 receptor is coupled to regulation of apoptosis and ERK1/2 activation through divergent signaling pathways
    J A Koehler
    Department of Medicine, General Hospital, Banting and Best Diabetes Centre, 200 Elizabeth Street, MBRW4R 402, Toronto, Canada M5G 2C4
    Mol Endocrinol 19:459-73. 2005
    ....
  39. ncbi Essential requirement for Pax6 in control of enteroendocrine proglucagon gene transcription
    M E Hill
    Department of Medicine, The Banting and Best Diabetes Centre, Toronto General Hospital, Ontario, Canada
    Mol Endocrinol 13:1474-86. 1999
    ..These findings implicate an essential role for Pax6 in the development and function of glucagon-producing cells in both pancreatic and intestinal endodermal lineages...
  40. ncbi Cellular specificity of proexendin-4 processing in mammalian cells in vitro and in vivo
    F A Adatia
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Endocrinology 143:3464-71. 2002
    ..These findings may be useful for engineering cells that express a lizard pro-Ex4 transgene for the treatment of type 2 diabetes...
  41. ncbi Differential importance of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide 1 receptor signaling for beta cell survival in mice
    Adriano Maida
    Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Gastroenterology 137:2146-57. 2009
    ....
  42. ncbi beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1
    Yazhou Li
    Department of Medicine, University of Toronto, Banting and Best Diabetes Centre, Toronto General Hospital, 200 Elizabeth St, MBRW 4R402 2, Toronto, Canada M5G 2C4
    Diabetes 54:482-91. 2005
    ..These findings demonstrate that Pdx1 expression is essential for integrating GLP-1R-dependent signals regulating alpha-cell glucagon secretion and for the growth, differentiated function, and survival of islet beta-cells...
  43. ncbi Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo
    Jung Guk Kim
    Banting and Best Diabetes Centre, Department of Medicine, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4
    Diabetes 52:751-9. 2003
    ..These findings demonstrate that an albumin-conjugated DAC:GLP-1 mimics the action of native GLP-1 and represents a new approach for prolonged activation of GLP-1R signaling...
  44. ncbi Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene
    L A Scrocchi
    Department of Medicine, University of Toronto, Ontario
    Nat Med 2:1254-8. 1996
    ....
  45. ncbi Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling
    N J MacLusky
    Department of Reproductive Science, University of Toronto, Ontario, Canada
    Endocrinology 141:752-62. 2000
    ....
  46. ncbi Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system
    P L Brubaker
    Room 3366, Medical Science Building, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Endocrinology 145:2653-9. 2004
    ..These proliferative and antiapoptotic actions of GLP-1 and GLP-2 may contribute to protective and regenerative actions of these peptides in human subjects with diabetes and intestinal disorders, respectively...
  47. ncbi Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors
    P L Brubaker
    Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario, Canada
    Receptors Channels 8:179-88. 2002
    ..This article provides an overview of the biology of these receptors with an emphasis on understanding the unique actions of glucagon-related peptides through studies of the biology of their cognate receptors...
  48. ncbi Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor
    R P Boushey
    Department of Medicine, University Health Network, Toronto General Hospital, Ontario, Canada
    Cancer Res 61:687-93. 2001
    ..These observations demonstrate that the antiapoptotic effects of GLP-2 on intestinal crypt cells may be useful for the attenuation of chemotherapy-induced intestinal mucositis...
  49. ncbi Enteroendocrine localization of GLP-2 receptor expression in humans and rodents
    B Yusta
    Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
    Gastroenterology 119:744-55. 2000
    ..GLP-2 acts via binding to a single G protein-coupled GLP-2 receptor (GLP-2R), but the cellular targets for the diverse actions of GLP-2 remain unknown...
  50. ncbi GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice
    Tanya Hansotia
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, and the University of Toronto, 200 Elizabeth Street MBRW4R 402, Toronto, Ontario, Canada M5G 2C4
    Regul Pept 128:125-34. 2005
    ..Hence, incretin receptor signaling exerts physiologically relevant actions critical for glucose homeostasis, and represents a pharmacologically attractive target for development of agents for the treatment of Type 2 diabetes...
  51. ncbi Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis
    Yazhou Li
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario M5G 2C4, Canada
    J Biol Chem 278:471-8. 2003
    ....
  52. doi An albumin-exendin-4 conjugate engages central and peripheral circuits regulating murine energy and glucose homeostasis
    Laurie L Baggio
    Department of Medicine, Mt Sinai Hospital, Toronto, Ontario, Canada
    Gastroenterology 134:1137-47. 2008
    ....
  53. ncbi Effects of aging and a high fat diet on body weight and glucose tolerance in glucagon-like peptide-1 receptor -/- mice
    L A Scrocchi
    Department of Medicine, Banting and Best Diabetes Center, Toronto Hospital, University of Toronto, Ontario, Canada
    Endocrinology 139:3127-32. 1998
    ..These observations demonstrate that long term disruption of GLP-1 signaling in the central nervous system and peripheral tissues of older mice is not associated with the development of obesity or deterioration in glucose homeostasis...
  54. ncbi Proglucagon gene expression is induced by gastrin-releasing peptide in a mouse enteroendocrine cell line
    F Lu
    Department of Medicine, Banting and Best Diabetes Center, Toronto Hospital, University of Toronto, Ontario, Canada
    Endocrinology 137:3710-6. 1996
    ..These observations identify GRP as a peptide activator of proglucagon gene expression and provide evidence linking the proglucagon gene CRE to the physiological control of proglucagon gene expression...
  55. ncbi The LIM domain homeobox gene isl-1: conservation of human, hamster, and rat complementary deoxyribonucleic acid sequences and expression in cell types of nonneuroendocrine lineage
    M Wang
    Department of Clinical Biochemistry, Toronto General Hospital, University of Toronto, Ontario, Canada
    Endocrinology 134:1416-22. 1994
    ..These experiments suggest that the biological importance of isl-1 may not be restricted to neuroendocrine cell lineages and raise the possibility that isl-1 function may be regulated by sequestration in distinct cellular compartments...
  56. ncbi Proglucagon-derived peptides: mechanisms of action and therapeutic potential
    Elaine M Sinclair
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital and the University of Toronto, Toronto, Ontario, Canada
    Physiology (Bethesda) 20:357-65. 2005
    ..This review discusses the physiological, pharmacological, and therapeutic actions of the proglucagon-derived peptides, with an emphasis on clinical relevance of the peptides for the treatment of human disease...
  57. ncbi Human glucagon gene promoter sequences regulating tissue-specific versus nutrient-regulated gene expression
    Min Nian
    Department of Laboratory Medicine and Pathobiology, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Canada M5G 2C4
    Am J Physiol Regul Integr Comp Physiol 282:R173-83. 2002
    ....
  58. ncbi Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure
    Laurie L Baggio
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada
    Gastroenterology 127:546-58. 2004
    ..The proglucagon-derived peptide (PGDP) oxyntomodulin (OXM) is cosecreted with GLP-1 and inhibits feeding in rodents and humans; however, a distinct receptor for OXM has not been identified...
  59. ncbi Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells
    I Hadjiyanni
    Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue TCP5 1004, Toronto, ON M5G 1X5, Canada
    Diabetologia 53:730-40. 2010
    ..However, there is little information on the role of the GLP-1R in the immune system. We studied the role of the GLP-1R in immune function in wild-type (WT) and nonobese diabetic (NOD) and Glp1r-/- mice...
  60. ncbi Circulating and tissue forms of the intestinal growth factor, glucagon-like peptide-2
    P L Brubaker
    Department of Physiology, University of Toronto, Ontario, Canada
    Endocrinology 138:4837-43. 1997
    ..Thus, while GLP-2-(1-33) is a major circulating and tissue form of GLP-2, GLP-2-(3-33) is a significant component ofimmunoreactive GLP-2 in both intestine and plasma...
  61. doi Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice
    A Maida
    Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
    Diabetologia 54:339-49. 2011
    ..We examined whether metformin exerts glucoregulatory actions via modulation of the incretin axis...
  62. ncbi Leptin sensitivity in nonobese glucagon-like peptide I receptor -/- mice
    L A Scrocchi
    Department of Medicine, Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto, Canada
    Diabetes 46:2029-34. 1997
    ..Furthermore, the greater effects of leptin on glucose and insulin in leptin-treated versus pair-fed GLP-IR -/- mice raises the possibility that disruption of GLP-I signaling modifies the sensitivity to leptin in vivo...
  63. ncbi Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line
    P L Brubaker
    Department of Physiology, Toronto Hospital, and Banting and Best Diabetes Center, University of Toronto, Ontario, Canada
    Endocrinology 139:4108-14. 1998
    ..Therefore, by comparison with results obtained using primary L cell cultures or in vivo models, GLUTag cells appear to respond appropriately to the regulatory mechanisms controlling intestinal GLP-1 secretion...
  64. ncbi A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis
    Laurie L Baggio
    Toronto General Hospital, Banting and Best Diabetes Centre, 200 Elizabeth St, MBRW4R 402, Toronto, Canada
    Diabetes 53:2492-500. 2004
    ..These findings illustrate that peripheral administration of a larger peptide-albumin recombinant protein mimics GLP-1R-dependent activation of central and peripheral pathways regulating energy intake and glucose homeostasis in vivo...
  65. doi Acute dipeptidyl peptidase-4 inhibition rapidly enhances insulin-mediated suppression of endogenous glucose production in mice
    Hélène Duez
    Department of Medicine and Physiology, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada
    Endocrinology 150:56-62. 2009
    ..These findings illustrate that DPP-4 inhibition modulates glucose homeostasis through pathways distinct from those used by GLP-1R agonists in mice...
  66. ncbi Incretin receptors for glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide are essential for the sustained metabolic actions of vildagliptin in mice
    Grace Flock
    Samuel Lunenfeld Research Institute, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada
    Diabetes 56:3006-13. 2007
    ....
  67. ncbi Pax-2 activates the proglucagon gene promoter but is not essential for proglucagon gene expression or development of proglucagon-producing cell lineages in the murine pancreas or intestine
    Grace Flock
    The Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4
    Mol Endocrinol 16:2349-59. 2002
    ..These findings demonstrate that Pax-2 is not essential for the developmental formation of islet A or gut L cells and does not play a role in the physiological control of proglucagon gene expression in vivo...
  68. ncbi Mucosal adaptation to enteral nutrients is dependent on the physiologic actions of glucagon-like peptide-2 in mice
    Eric D Shin
    Department of Physiology, University of Toronto, Ontario, Canada
    Gastroenterology 128:1340-53. 2005
    ..However, the physiologic role of GLP-2 in mucosal growth and adaptation to nutritional stimulation remains poorly understood...
  69. ncbi Pdx-1 is not sufficient for repression of proglucagon gene transcription in islet or enteroendocrine cells
    Grace Flock
    Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
    Endocrinology 146:441-9. 2005
    ..Taken together, these findings demonstrate that pdx-1 alone is not sufficient for specification of the hormonal phenotype or extinction of proglucagon gene expression in islet or enteroendocrine cells...
  70. ncbi Clinical endocrinology and metabolism. Glucagon-like peptide-1 and glucagon-like peptide-2
    Laurie L Baggio
    Department of Medicine, The Banting and Best Diabetes Centre, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, MBRW 4R 402, Toronto, Ontario, Canada M5G 2C4
    Best Pract Res Clin Endocrinol Metab 18:531-54. 2004
    ..This review will highlight our current understanding of the biology of GLP-1 and GLP-2, with an emphasis on both well-characterized and more novel therapeutic applications of these peptides...
  71. ncbi Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1
    J Dong
    Department of Medicine, University of Toronto, Ontario, Canada
    Mol Endocrinol 5:1633-41. 1991
    ..The results of these studies implicate a potential role for isl-1 outside the endocrine pancreas in the nervous system and kidney...
  72. ncbi Glucagon gene expression in vertebrate brain
    D J Drucker
    Department of Medicine, Toronto General Hospital, Ontario, Canada
    J Biol Chem 263:13475-8. 1988
    ..We now report that the glucagon gene is expressed in the brainstem and hypothalamus and that a glucagon mRNA transcript identical to that produced in pancreas and intestine gives rise to proglucagon-related peptides in the brain...
  73. ncbi Differential antidiabetic efficacy of incretin agonists versus DPP-4 inhibition in high fat fed mice
    Benjamin J Lamont
    Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Diabetes 57:190-8. 2008
    ....
  74. ncbi Glucagon-like peptide-2 receptor modulates islet adaptation to metabolic stress in the ob/ob mouse
    Jasmine Bahrami
    Department of Medicine, Mt Sinai Hospital, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada
    Gastroenterology 139:857-68. 2010
    ..We examined the importance of GLP-2 receptor (GLP-2R) signaling for glucose homeostasis in multiple models of metabolic stress, diabetes, and obesity...
  75. ncbi GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress
    Bernardo Yusta
    Department of Medicine, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Cell Metab 4:391-406. 2006
    ..These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival...
  76. ncbi Hypoglycemia, defective islet glucagon secretion, but normal islet mass in mice with a disruption of the gastrin gene
    Robin P Boushey
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
    Gastroenterology 125:1164-74. 2003
    ..Although gastrin action has been linked to islet neogenesis, transdifferentiation, and beta-cell regeneration, an essential physiologic role(s) for gastrin in the pancreas has not been established...
  77. ncbi Lymphocytic infiltration and immune activation in metallothionein promoter-exendin-4 (MT-Exendin) transgenic mice
    Laurie L Baggio
    Department of Medicine, Banting and Best Deabetes Centre, Toronto General Hospital, 200 Elizabeth St, MBRW4R 402, Toronto, Ontario, Canada M5G2C4
    Diabetes 55:1562-70. 2006
    ..These findings demonstrate that expression of a proexendin-4 transgene may be associated with activation of humoral and cellular immune responses in mice...
  78. pmc Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMP-activated protein kinase-related protein kinase, SNARK
    D L Lefebvre
    Department of Medicine, Division of Dermatology, Toronto General Hospital, Banting Institute, Room 317, 100 College Street, Toronto M5G 1L5, Ontario, Canada
    Biochem J 355:297-305. 2001
    ..These findings identify SNARK as a glucose- and AICAriboside-regulated member of the AMPK-related gene family that represents a new candidate mediator of the cellular response to metabolic stress...
  79. ncbi Glucagon and glucagon-like peptide receptors as drug targets
    J L Estall
    Department of Laboratory Medicine and Pathobiology, and Medicine, University of Toronto, The Banting and Best Diabetes Centre, Toronto General Hospital, Canada
    Curr Pharm Des 12:1731-50. 2006
    ..Taken together, the separate receptors for glucagon, GLP-1, and GLP-2 represent important targets for developing novel therapeutic agents for the treatment of disorders of energy homeostasis...
  80. doi The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice
    J Hsieh
    Department of Biochemistry, University of Toronto, Toronto, ON, Canada
    Diabetologia 53:552-61. 2010
    ..As dyslipidaemia is a contributing risk factor for cardiovascular disease in type 2 diabetes, we examined the mechanisms linking pharmacological and physiological regulation of GLP-1 action to control of postprandial lipid metabolism...
  81. ncbi Aberrant regulation of human intestinal proglucagon gene expression in the NCI-H716 cell line
    Xiemin Cao
    Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Canada M5G 2C4
    Endocrinology 144:2025-33. 2003
    ..Hence, NCI-H716 cells may not be a physiologically optimal model for studies of human enteroendocrine proglucagon gene transcription...
  82. ncbi Prolonged gastrointestinal transit in a patient with a glucagon-like peptide (GLP)-1- and -2-producing neuroendocrine tumor
    Patricia L Brubaker
    Departments of Physiology, University of Toronto, Room 3366 Medical Sciences Building, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    J Clin Endocrinol Metab 87:3078-83. 2002
    ..Overexpression of glucagon-like peptide-1 and -2 is associated with markedly prolonged gastrointestinal transit in humans. These findings are consistent with a role for these peptides in the regulation of gastrointestinal motility...
  83. ncbi Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa
    Natalie A Walsh
    Department of Physiology, University of Toronto, Toronto, Canada M5S 1A8
    Endocrinology 144:4385-92. 2003
    ..These results provide the first evidence that activation of the endogenous rat mucosal GLP-2 receptor is linked to activation of a cAMP/protein kinase A-dependent, growth-promoting pathway in vitro...
  84. doi Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study
    Daniel J Drucker
    Department of Medicine, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada
    Lancet 372:1240-50. 2008
    ..We compared the efficacy of a once-weekly formulation of exenatide to that of a twice daily dose...
  85. ncbi Ciliary neurotrophic factor recruitment of glucagon-like peptide-1 mediates neurogenesis, allowing immortalization of adult murine hypothalamic neurons
    Denise D Belsham
    Department of Physiology, University of Toronto, Medical Sciences Bldg 3247A, 1 King s College Cir, Toronto, ON M5S1A8, Canada
    FASEB J 23:4256-65. 2009
    ....
  86. ncbi Activation of glucagon-like peptide-1 receptor signaling does not modify the growth or apoptosis of human pancreatic cancer cells
    Jacqueline A Koehler
    Banting and Best Diabetes Centre, Toronto General Hospital, 200 Elizabeth St MBRW4R 402, Toronto, Ontario, Canada M5G 2C4
    Diabetes 55:1369-79. 2006
    ..Thus, acute or chronic (4 weeks) GLP-1R stimulation does not modify the growth or survival of human pancreatic cancer cells...
  87. ncbi Pax-6 activates endogenous proglucagon gene expression in the rodent gastrointestinal epithelium
    Denny K Y Trinh
    Department of Medicine, Banting and Best Diabetes Center, Toronto General Hospital, University of Toronto, Ontario, Canada
    Diabetes 52:425-33. 2003
    ..These data demonstrate that Pax-6, but not Cdx-2/3, is capable of activating the endogenous proglucagon gene in both immortalized enteroendocrine cells and the nontransformed intestinal epithelium in vivo...
  88. pmc Foxa3 (HNF-3gamma) binds to and activates the rat proglucagon gene promoter but is not essential for proglucagon gene expression
    Yuanfang Liu
    Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, 101 College Street CCRW3 845, Toronto, Canada M5G 2C4
    Biochem J 366:633-41. 2002
    ..These findings identify Foxa3 as a member of the proglucagon gene G2 element binding-protein family that, unlike Foxa1, is not essential for control of islet or intestinal proglucagon gene expression in vivo...
  89. ncbi Biology of incretins: GLP-1 and GIP
    Laurie L Baggio
    Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
    Gastroenterology 132:2131-57. 2007
    ..Recently approved therapeutic agents based on potentiation of incretin action provide new physiologically based approaches for the treatment of type 2 diabetes...
  90. pmc Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure
    Tanya Hansotia
    Banting and Best Diabetes Centre, Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    J Clin Invest 117:143-52. 2007
    ..These findings extend our understanding of how endogenous incretin circuits regulate glucose homeostasis independent of the beta cell via control of adipokine secretion and energy expenditure...
  91. ncbi Enhancing the action of incretin hormones: a new whey forward?
    Daniel J Drucker
    Department of Medicine and The Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4
    Endocrinology 147:3171-2. 2006
  92. ncbi Differential expression of RNA transcripts encoding unique carboxy-terminal sequences of human parathyroid hormone-related peptide
    R V Campos
    Department of Medicine, University of Toronto, Ontario, Canada
    Mol Endocrinol 8:1656-66. 1994
    ..These studies suggest that exon splicing at the 3'-end of the hPTHrP gene may be an important determinant of the biological complexity of hPTHrP gene expression...
  93. pmc Normalization of obesity-associated insulin resistance through immunotherapy
    Shawn Winer
    Department of Pediatrics and Immunology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Nat Med 15:921-9. 2009
    ..The eventual failure of this control, with expanding adiposity and pathogenic VAT T cells, can successfully be reversed by immunotherapy...
  94. ncbi Glucagon receptor signaling is essential for control of murine hepatocyte survival
    Elaine M Sinclair
    Department of Medicine, Mt Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada
    Gastroenterology 135:2096-106. 2008
    ....
  95. doi Glucagon-like peptide (GLP)-1(9-36)amide-mediated cytoprotection is blocked by exendin(9-39) yet does not require the known GLP-1 receptor
    Kiwon Ban
    TMDT 3 904, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4
    Endocrinology 151:1520-31. 2010
    ..the GLP-1R agonist exendin-4 and reveal the existence of a GLP-1(9-36)amide-responsive, exendin(9-39)-sensitive, cardioprotective signaling pathway distinct from that associated with the classical GLP-1 receptor...
  96. pmc Tissue-specific role of glycogen synthase kinase 3beta in glucose homeostasis and insulin action
    Satish Patel
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Mol Cell Biol 28:6314-28. 2008
    ..These data indicate that there are not only distinct roles for GSK-3alpha and GSK-3beta within the adult but also tissue-specific phenotypes associated with each of these isoforms...
  97. doi Intensive insulin therapy in newly diagnosed type 2 diabetes
    Ravi Retnakaran
    Division of Endocrinology, University of Toronto, Toronto, Ont, Canada M5G 1X5
    Lancet 371:1725-6. 2008
  98. ncbi Harnessing the therapeutic potential of glucagon-like peptide-1: a critical review
    Laurie L Baggio
    Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    Treat Endocrinol 1:117-25. 2002
    ..Hence, orally available DPP-IV inhibitors also represent a new class of therapeutic agents that enhance incretin action for the treatment of patients with type 2 diabetes mellitus...
  99. ncbi The glucagon-like peptide-1 receptor agonist oxyntomodulin enhances beta-cell function but does not inhibit gastric emptying in mice
    Adriano Maida
    Mt Sinai Hospital, Samuel Lunenfeld Research Institute, 60 Murray Street, Toronto, Ontario, Canada M5G 1X5
    Endocrinology 149:5670-8. 2008
    ..These findings may have implications for therapeutic efforts using OXM as a long-acting GLP-1R agonist for the treatment of metabolic disorders...