Research Topics
Genomes and Genes
| James D JohnsonSummaryAffiliation: University of British Columbia Country: Canada Publications
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Detail Information
Publications
Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteomeJames D Johnson
Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
Proc Natl Acad Sci U S A 103:19575-80. 2006..Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses. Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1...- Control of pancreatic beta-cell fate by insulin signaling: The sweet spot hypothesisJames D Johnson
Laboratory of Molecular Signalling in Diabetes, Life Sciences Institute, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
Cell Cycle 7:1343-7. 2008..We also highlight the key experiments that are required to further test this hypothesis... - Suppressed insulin signaling and increased apoptosis in CD38-null isletsJames D Johnson
Division of Metabolism, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA
Diabetes 55:2737-46. 2006..Thus, our results suggest that CD38 plays a role in novel antiapoptotic signaling pathways but does not directly control glucose signaling in pancreatic beta-cells... - Proteomic identification of carboxypeptidase E connects lipid-induced beta-cell apoptosis and dysfunction in type 2 diabetesJames D Johnson
Laboratory of Molecular Signalling in Diabetes, Life Sciences Institute, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
Cell Cycle 8:38-42. 2009..These newly identified targets of beta-cell lipotoxicity present novel avenues for research and therapeutic intervention... - Different effects of FK506, rapamycin, and mycophenolate mofetil on glucose-stimulated insulin release and apoptosis in human isletsJames D Johnson
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
Cell Transplant 18:833-45. 2009..Together, our results demonstrate that immunosuppressants impair human beta-cell function and survival, and that these defects can be circumvented to a certain extent with exenatide treatment... - Mechanisms of pancreatic beta-cell apoptosis in diabetes and its therapiesJames D Johnson
Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3
Adv Exp Med Biol 654:447-62. 2010..In this chapter, we review the factors that influence the propensity of beta-cells to undergo apoptosis and the mechanisms of this programmed cell death in the initiation and progression of diabetes... - Impaired insulin secretion in transgenic mice over-expressing calpastatin in pancreatic ?-cellsJames D Johnson
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
Islets 1:242-8. 2009..These studies provide the first evidence that blocking endogenous calpain activity partially impairs insulin release in vivo and in vitro by targeting distal components of the insulin exocytotic machinery... - Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and beta-cell deathDan S Luciani
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Comlumbia, Canada
Diabetes 58:422-32. 2009..Here, we examined the effects of stimulating or inhibiting the ER-resident inositol trisphosphate receptors (IP(3)Rs) and the ryanodine receptors (RyRs) on the induction of beta-cell ER stress and apoptosis... - RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic isletsJames D Johnson
Department of Internal Medicine, Washington University, St Louis, Missouri 63110, USA
J Biol Chem 279:24794-802. 2004..Thus RyR2 activity seems to play an essential role in beta-cell survival in vitro by suppressing a death pathway mediated by calpain-10, a type 2 diabetes susceptibility gene with previously unknown function... - Glucose and endoplasmic reticulum calcium channels regulate HIF-1beta via presenilin in pancreatic beta-cellsVardit Dror
Laboratory of Molecular Signaling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
J Biol Chem 283:9909-16. 2008..These findings provide a mechanistic understanding of the signaling pathways activated when intracellular Ca(2+) homeostasis and metabolic activity are suppressed in diabetes and islet transplantation... - Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosisKristin D Jeffrey
Diabetes Research Group, Laboratory of Molecular Signalling in Diabetes, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
Proc Natl Acad Sci U S A 105:8452-7. 2008..Thus, carboxypeptidase E degradation contributes to palmitate-induced beta-cell ER stress and apoptosis. CPE is a major link between hyperlipidemia and beta-cell death pathways in diabetes... - Glucose-induced endothelial heparanase secretion requires cortical and stress actin reorganizationFang Wang
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146, East Mall, Vancouver, BC, Canada V6T 1Z3
Cardiovasc Res 87:127-36. 2010..Using high glucose (HG) to replicate hyperglycaemia observed following diabetes, the present study was designed to determine the mechanism by which HG initiates endothelial heparanase secretion... - Reduced expression of the insulin receptor in mouse insulinoma (MIN6) cells reveals multiple roles of insulin signaling in gene expression, proliferation, insulin content, and secretionMitsuru Ohsugi
Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 280:4992-5003. 2005..These results demonstrate important roles of the insulin receptor in islet beta cell gene expression and function and may serve to elucidate molecular defects in animal models with diminished beta cell insulin signaling... - Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretionJames D Johnson
Division of Metabolism, Department of Internal Medicine, Washington University School of Medicine, Box 8126, 8831 Wohl Clinic, 660 S Euclid, St Louis, MO 63110, USA
FASEB J 18:878-80. 2004.... - Increased islet apoptosis in Pdx1+/- miceJames D Johnson
Renal Division, Department of Internal Medicine, Washington University School of Medicine Barnes Jewish Hospital, 660 S Euclid Avenue, St Louis, MO 63110, USA
J Clin Invest 111:1147-60. 2003.... - Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cellsErnesto Bernal-Mizrachi
Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 114:928-36. 2004..These observations suggest that Akt plays a novel and important role in the regulation of distal components of the secretory pathway and that this enzyme represents a therapeutic target for improvement of beta cell function in diabetes... - Acute insulin signaling in pancreatic beta-cells is mediated by multiple Raf-1 dependent pathwaysEmilyn U Alejandro
Department of Cellular and Physiological Sciences, University of British Columbia, 5358 Life Sciences Building, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada
Endocrinology 151:502-12. 2010..Together our findings identify a novel insulin signaling pathway in beta-cells and shed light on insulin's antiapoptotic and mitogenic mechanisms... - Kinetics and genomic profiling of adult human and mouse ?-cell maturationMarta Szabat
Laboratory of Molecular Signaling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
Islets 3:175-87. 2011..The results have significant implications for islet regeneration and for in vitro generation of functional ?-cells to treat diabetes... - Fatty acid-induced nuclear translocation of heparanase uncouples glucose metabolism in endothelial cellsFang Wang
Molecular and Cellular Pharmacology Group, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, B C, Canada V6T 1Z3
Arterioscler Thromb Vasc Biol 32:406-14. 2012..We have recently reported that high fatty acid increased the nuclear content of endothelial heparanase. Here, we examined the mechanism and the consequences behind this nuclear translocation of heparanase... - A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetesGarth L Warnock
Departments of Surgery, Ophthalmology and Visual Sciences, and Medicine, Ike Barber Human Islet Transplantation Laboratory, University of British Columbia, Vancouver, BC, Canada
Transplantation 86:1762-6. 2008..We hypothesized that transplantation of islets into type 1 diabetics could improve outcomes of glucose metabolism, renal function, retinopathy, and neuropathy compared with intensive medical therapy... - Differential regulation and localization of carboxypeptidase D and carboxypeptidase E in human and mouse ?-cellsKwan Yi Chu
Laboratory of Molecular Signaling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
Islets 3:155-65. 2011..Taken together, our data demonstrate that CPE and CPD are differentially localized, differentially regulated and unlikely to have compensatory functions in pancreatic ?-cells... - Voltage-gated Ca(2+) influx and insulin secretion in human and mouse beta-cells are impaired by the mitochondrial Na(+)/Ca(2+) exchange inhibitor CGP-37157Dan S Luciani
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
Eur J Pharmacol 576:18-25. 2007..Efforts to use CGP-37157 or design related compounds for therapeutic purposes should take these competing effects into account... - Autophagy regulates pancreatic beta cell death in response to Pdx1 deficiency and nutrient deprivationKei Fujimoto
Division of Endocrinology, Metabolism and Lipid Research, Department of Internal Medicine, Washington University School of Medicine Barnes Jewish Hospital, St Louis, Missouri 63110, USA
J Biol Chem 284:27664-73. 2009..The role of autophagy should be considered in studies of pancreatic beta cell death and diabetes and as a target for novel therapeutic intervention... - Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirusMarta Szabat
Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
Endocrinology 150:1627-35. 2009..These results have implications for harnessing the maturation process for therapeutic purposes... - Improved human pancreatic islet isolation for a prospective cohort study of islet transplantation vs best medical therapy in type 1 diabetes mellitusGarth L Warnock
Department of Surgery, British Columbia Islet Transplant Centre, University of British Columbia, 950 W 10th Avenue, Vancouver, BC, Canada V5Z 4E3
Arch Surg 140:735-44. 2005..A local multiorgan donor pancreas procurement program can provide a source for optimized isolation of purified viable islets for transplantation into patients with type 1 diabetes mellitus receiving best medical therapy... - Effects of palmitate on ER and cytosolic Ca2+ homeostasis in beta-cellsKamila S Gwiazda
Laboratory of Molecular Signaling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, 5358 Life Sciences Bldg, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3
Am J Physiol Endocrinol Metab 296:E690-701. 2009..We present the first direct evidence that free fatty acids reduce ER Ca2+ and shed light on pathways involved in lipotoxicity and the pathogenesis of type 2 diabetes... - Pancreatic ?-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcriptionEmilyn U Alejandro
Laboratory of Molecular Signalling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
FASEB J 25:3884-95. 2011..This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo... - Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1)Rhonda D Wideman
Laboratories of Molecular and Cellular Medicine, Departments of Cellular and Physiological Sciences and Surgery, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada
Proc Natl Acad Sci U S A 103:13468-73. 2006..These results demonstrate a unique strategy for liberating GLP-1 from directly within the target organ and highlight the potential for up-regulating islet GLP-1 production as a means of treating diabetes... - Insulin stimulates primary beta-cell proliferation via Raf-1 kinaseJennifer L Beith
Laboratory of Molecular Signalling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
Endocrinology 149:2251-60. 2008..These findings have significant implications for the understanding of the regulation of beta-cell mass in both the hyperinsulinemic and insulin-deficient states that occur in the various forms of diabetes... - A multi-parameter, high-content, high-throughput screening platform to identify natural compounds that modulate insulin and Pdx1 expressionJessica A Hill
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
PLoS ONE 5:e12958. 2010..This work represents an important step towards the development of drugs to increase insulin expression in diabetes and during in vitro differentiation of beta-cell replacements... - Acute effects of insulin on beta-cells from transplantable human isletsDan S Luciani
Department of Cellular and Physiological Science, University of British Columbia, Vancouver, 2350 Health Sciences Mall, Vancouver, BC, Canada
Mol Cell Endocrinol 241:88-98. 2005..Our findings suggest autocrine insulin signaling directly controls insulin protein levels, but not exocytosis, in beta-cells and demonstrate the functional specificity of insulin signaling and glucose signaling in human islet cells... - Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatmentLiam R Brunham
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada
Nat Med 13:340-7. 2007..These experiments establish a new role for Abca1 in beta-cell cholesterol homeostasis and insulin secretion, and suggest that cholesterol accumulation may contribute to beta-cell dysfunction in type 2 diabetes... - ATP-citrate lyase reduction mediates palmitate-induced apoptosis in pancreatic beta cellsKwan Yi Chu
Laboratory of Molecular Signaling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
J Biol Chem 285:32606-15. 2010..These findings add to the emerging body of evidence linking beta cell metabolism with programmed cell death... - Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelationCorinne A Hoesli
Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, Canada
Biotechnol Bioeng 108:424-34. 2011.... - Rheb activates protein synthesis and growth in adult rat ventricular cardiomyocytesYanni Wang
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
J Mol Cell Cardiol 45:812-20. 2008..Our findings reveal that Rheb itself can activate both protein synthesis and cell growth in ARVC and demonstrate the key role played by mTORC1 in the growth of cardiomyocytes... - MISC-1/OGC links mitochondrial metabolism, apoptosis and insulin secretionMarco Gallo
Department of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada
PLoS ONE 6:e17827. 2011..Our results suggest that controlling MISC-1/OGC function allows regulation of mitochondrial morphology and cell survival decisions by the metabolic needs of the cell... - Loss of Both ABCA1 and ABCG1 Results in Increased Disturbances in Islet Sterol Homeostasis, Inflammation, and Impaired ?-Cell FunctionJanine K Kruit
Corresponding author Michael R Hayden
Diabetes 61:659-64. 2012..These data suggest that ABCA1 and ABCG1 each make complimentary and important contributions to ?-cell function by maintaining islet cholesterol homeostasis in vivo... - Role of the TLR signaling molecule TRIF in ?-cell function and glucose homeostasisMeredith J H Hutton
Department of Pathology and Laboratory Medicine, University of British Columbia, Child and Family Research Institute, Vancouver, Canada
Islets 2:104-11. 2010..These studies suggest a role for TLR signaling in glucose homeostasis, and raise the possibility that TRIF signaling is required for normal b-cell function... - Ontogeny of ghrelin, obestatin, preproghrelin, and prohormone convertases in rat pancreas and stomachPallavi Walia
Endocrinology and Diabetes Unit, British Columbia Children s Hospital, Vancouver, British Columbia, V6H 3V4, Canada
Pediatr Res 65:39-44. 2009..In pancreas, the colocalization of PC1/3 or PC2 in ghrelin positive cells points to a role for both PCs in preproghrelin processing... - AMP-activated protein kinase confers protection against TNF-{alpha}-induced cardiac cell deathGirish Kewalramani
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada
Cardiovasc Res 84:42-53. 2009.... - An odyssey of islet transplantation for therapy of type 1 diabetesGarth L Warnock
Department of Surgery, University of British Columbia Medical Center, 910 West 10th Avenue, Vancouver, British Columbia V5Z 4E3
World J Surg 31:1569-76. 2007..In this article, some seminal Canadian contributions to this field are reviewed, including contributions at the basic research laboratory and translational applications to bedside therapy of type 1 diabetes... - Inhibition of Raf-1 alters multiple downstream pathways to induce pancreatic beta-cell apoptosisEmilyn U Alejandro
Laboratory of Molecular Signaling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
J Biol Chem 283:2407-17. 2008..These studies identify Raf-1 as a critical anti-apoptotic kinase in pancreatic beta-cells and contribute to our understanding of survival signaling in this cell type... - Purified human pancreatic duct cell culture conditions defined by serum-free high-content growth factor screeningCorinne A Hoesli
Michael Smith Laboratories and Department of Biological and Chemical Engineering, University of British Columbia, Vancouver, Canada
PLoS ONE 7:e33999. 2012..The methods developed in this work should advance pancreatic cancer and diabetes research by providing effective cell culture and high-throughput screening platforms to study purified primary pancreatic CK19+ cells... - Nicotinic acid-adenine dinucleotide phosphate-sensitive calcium stores initiate insulin signaling in human beta cellsJames D Johnson
Department of Internal Medicine, Renal Division, Barnes Jewish Hospital, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 99:14566-71. 2002..These data reveal the complexity of insulin signal transduction and function in human beta cells and demonstrate functional NAADP-sensitive Ca(2+) stores in a human primary cultured cell type... - Nanospaces between endoplasmic reticulum and mitochondria as control centres of pancreatic ?-cell metabolism and survivalJames D Johnson
Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3
Protoplasma 249:49-58. 2012..Many aspects of the mechanisms underlying this control system remain to be uncovered, and new nanotechnologies are required understand these domains at a molecular level...