M Cnop

Summary

Country: Belgium

Publications

  1. ncbi request reprint RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate
    Miriam Cnop
    Laboratory of Experimental Medicine, ULB Center for Diabetes Research, Universite Libre de Bruxelles, Brussels, BelgiumDivision of Endocrinology, Erasmus Hospital, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 63:1978-93. 2014
  2. pmc Glucagon-like peptide-1 agonists protect pancreatic beta-cells from lipotoxic endoplasmic reticulum stress through upregulation of BiP and JunB
    Daniel A Cunha
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 58:2851-62. 2009
  3. doi request reprint Diabetes in Friedreich ataxia
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    J Neurochem 126:94-102. 2013
  4. doi request reprint Central role and mechanisms of β-cell dysfunction and death in friedreich ataxia-associated diabetes
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Ann Neurol 72:971-82. 2012
  5. pmc Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β-cell apoptosis
    Daniel A Cunha
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 61:2763-75. 2012
  6. doi request reprint Endoplasmic reticulum stress, obesity and diabetes
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, CP 618, Route de Lennik 808, 1070 Brussels, Belgium
    Trends Mol Med 18:59-68. 2012
  7. doi request reprint An update on lipotoxic endoplasmic reticulum stress in pancreatic beta-cells
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, 808 Route de Lennik, 1070 Brussels, Belgium
    Biochem Soc Trans 36:909-15. 2008
  8. ncbi request reprint Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, 1070 Brussels, Belgium
    J Biol Chem 282:3989-97. 2007
  9. ncbi request reprint Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities
    Miriam Cnop
    Laboratory of Experimental Medicine, Faculty of Medicine, Erasmus Hospital, Universite Libre de Bruxelles ULB, Route de Lennik 808, CP 618, 1070 Brussels, Belgium
    Diabetes 54:S97-107. 2005
  10. doi request reprint Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, Division of Endocrinology, Erasmus Hospital, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Biochem Soc Trans 36:348-52. 2008

Collaborators

Detail Information

Publications38

  1. ncbi request reprint RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate
    Miriam Cnop
    Laboratory of Experimental Medicine, ULB Center for Diabetes Research, Universite Libre de Bruxelles, Brussels, BelgiumDivision of Endocrinology, Erasmus Hospital, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 63:1978-93. 2014
    ..This human islet transcriptome study identified novel mechanisms of palmitate-induced β-cell dysfunction and death. The data point to cross talk between metabolic stress and candidate genes at the β-cell level...
  2. pmc Glucagon-like peptide-1 agonists protect pancreatic beta-cells from lipotoxic endoplasmic reticulum stress through upregulation of BiP and JunB
    Daniel A Cunha
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 58:2851-62. 2009
    ..Here, we evaluated the molecular mechanisms involved in the protection of beta-cells from lipotoxic ER stress by glucagon-like peptide (GLP)-1 agonists utilized in the treatment of type 2 diabetes...
  3. doi request reprint Diabetes in Friedreich ataxia
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    J Neurochem 126:94-102. 2013
    ..A better understanding of the molecular mechanisms mediating β cell demise in Friedreich ataxia will pave the way for new therapeutic approaches. ..
  4. doi request reprint Central role and mechanisms of β-cell dysfunction and death in friedreich ataxia-associated diabetes
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Ann Neurol 72:971-82. 2012
    ..FRDA patients have a high prevalence of diabetes, the pathogenesis of which is not known. We aimed to evaluate the relative contribution of insulin resistance and β-cell failure and the pathogenic mechanisms involved in FRDA diabetes...
  5. pmc Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β-cell apoptosis
    Daniel A Cunha
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 61:2763-75. 2012
    ..This study elucidates the crosstalk between lipotoxic ER stress and the mitochondrial pathway of apoptosis that causes β-cell death in diabetes...
  6. doi request reprint Endoplasmic reticulum stress, obesity and diabetes
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, CP 618, Route de Lennik 808, 1070 Brussels, Belgium
    Trends Mol Med 18:59-68. 2012
    ..Finally, prolonged ER stress impairs insulin synthesis and causes pancreatic β cell apoptosis. In this review, we discuss ways in which ER stress operates as a common molecular pathway in the pathogenesis of obesity and diabetes...
  7. doi request reprint An update on lipotoxic endoplasmic reticulum stress in pancreatic beta-cells
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, 808 Route de Lennik, 1070 Brussels, Belgium
    Biochem Soc Trans 36:909-15. 2008
    ..In the present mini-review, we focus on recent progress in the field of ER stress in pancreatic beta-cells. Recent advances in the understanding of lipotoxic ER stress and beta-cell recovery from ER stress are discussed...
  8. ncbi request reprint Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, 1070 Brussels, Belgium
    J Biol Chem 282:3989-97. 2007
    ..This modifies the present paradigm regarding the beneficial role of eIF2alpha phosphorylation in beta-cells and must be taken into consideration when designing therapies to protect beta-cells in type 2 diabetes...
  9. ncbi request reprint Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities
    Miriam Cnop
    Laboratory of Experimental Medicine, Faculty of Medicine, Erasmus Hospital, Universite Libre de Bruxelles ULB, Route de Lennik 808, CP 618, 1070 Brussels, Belgium
    Diabetes 54:S97-107. 2005
    ..This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes...
  10. doi request reprint Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes
    Miriam Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, Division of Endocrinology, Erasmus Hospital, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Biochem Soc Trans 36:348-52. 2008
    ..A better understanding of the molecular mechanisms contributing to pancreatic beta-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes...
  11. doi request reprint Causes and cures for endoplasmic reticulum stress in lipotoxic β-cell dysfunction
    M Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, Brussels, Belgium
    Diabetes Obes Metab 12:76-82. 2010
    ..Chemical chaperones, salubrinal and glucagon-like peptide-1 (GLP-1) analogues have been used to protect β-cells from lipotoxic ER stress. Importantly, the pro- and antiapoptotic effects of these compounds are cell and context dependent...
  12. ncbi request reprint Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes
    M Igoillo-Esteve
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, CP 618, Route de Lennik 808, 1070, Brussels, Belgium
    Diabetologia 53:1395-405. 2010
    ..One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate...
  13. ncbi request reprint Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress
    Ilham Kharroubi
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, B 1070 Brussels, Belgium
    Endocrinology 145:5087-96. 2004
    ..Our results argue against a unifying hypothesis for the mechanisms of beta-cell death in T1DM and T2DM...
  14. ncbi request reprint Longevity of human islet α- and β-cells
    M Cnop
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, Brussels, Belgium
    Diabetes Obes Metab 13:39-46. 2011
    ..Induction of regeneration of human islet cells will require understanding of the mechanisms associated with age-related senescence...
  15. doi request reprint Enhanced signaling downstream of ribonucleic Acid-activated protein kinase-like endoplasmic reticulum kinase potentiates lipotoxic endoplasmic reticulum stress in human islets
    Laurence Ladriere
    Laboratory of Experimental Medicine, Université Libre de Bruxelles CP 618, Route de Lennik 808, 1070 Brussels, Belgium
    J Clin Endocrinol Metab 95:1442-9. 2010
    ..This should be taken into consideration when designing approaches to pharmacologically modulate the beta-cell ER stress response in type 2 diabetes...
  16. ncbi request reprint JunB protects β-cells from lipotoxicity via the XBP1-AKT pathway
    D A Cunha
    Laboratory of Experimental Medicine and ULB Center of Diabetes Research, Universite Libre de Bruxelles, Brussels, Belgium
    Cell Death Differ 21:1313-24. 2014
    ..These findings elucidate novel β-cell-protective signal transduction in type 2 diabetes. ..
  17. ncbi request reprint Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation
    M Cnop
    Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
    Diabetes 50:1771-7. 2001
    ..It is conceivable that this potential is lost or insufficient in cells with a prolonged triglyceride accumulation as may occur in vivo...
  18. ncbi request reprint The role for endoplasmic reticulum stress in diabetes mellitus
    Decio L Eizirik
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Endocr Rev 29:42-61. 2008
    ..A better understanding of the pathways regulating ER stress in beta-cells may be instrumental for the design of novel therapies to prevent beta-cell loss in diabetes...
  19. doi request reprint ER stress in pancreatic beta cells: the thin red line between adaptation and failure
    Decio L Eizirik
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, 1070 Brussels, Belgium
    Sci Signal 3:pe7. 2010
    ..These and other findings provide a first glimpse on how different signals trigger diverging UPR outcomes...
  20. pmc PTPN2, a candidate gene for type 1 diabetes, modulates interferon-gamma-induced pancreatic beta-cell apoptosis
    Fabrice Moore
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetes 58:1283-91. 2009
    ..We hypothesized that PTPN2 plays a direct role in beta-cell demise and assessed PTPN2 expression in human islets and rat primary and clonal beta-cells, besides evaluating its role in cytokine-induced signaling and beta-cell apoptosis...
  21. doi request reprint The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation
    M Cnop
    Laboratory of Experimental Medicine and Division of Endocrinology, Universite Libre de Bruxelles, Brussels, Belgium
    Diabetologia 53:321-30. 2010
    ..Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years...
  22. ncbi request reprint BCL-6: a possible missing link for anti-inflammatory PPAR-delta signalling in pancreatic beta cells
    I Kharroubi
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, CP 618, 808 Route de Lennik, Brussels, 1070, Belgium
    Diabetologia 49:2350-8. 2006
    ..PPAR-delta controls cellular lipid metabolism and is a major regulator of inflammatory responses. We therefore examined the role of PPAR-delta in cytokine-treated beta cells...
  23. ncbi request reprint Expression of adiponectin receptors in pancreatic beta cells
    Ilham Kharroubi
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Biochem Biophys Res Commun 312:1118-22. 2003
    ..Regulated adiponectin receptor expression on pancreatic beta cells might be a novel mechanism modulating the effects of circulating adiponectin...
  24. pmc Initiation and execution of lipotoxic ER stress in pancreatic beta-cells
    Daniel A Cunha
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    J Cell Sci 121:2308-18. 2008
    ..In conclusion, saturated FFA induce ER stress via ER Ca(2+) depletion. The IRE1 and resulting JNK activation contribute to beta-cell apoptosis. PERK activation by palmitate also contributes to beta-cell apoptosis via CHOP...
  25. pmc Endoplasmic reticulum stress sensitizes pancreatic beta cells to interleukin-1β-induced apoptosis via Bim/A1 imbalance
    M Miani
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, Brussels, Belgium
    Cell Death Dis 4:e701. 2013
    ..These findings link ER stress to exacerbated apoptosis during islet inflammation and provide potential mechanistic targets for beta cell protection, namely downregulation of Bim and upregulation of A1. ..
  26. doi request reprint Comparative pharmacoscintigraphic and pharmacokinetic evaluation of two new formulations of inhaled insulin in type 1 diabetic patients
    F Depreter
    Laboratory of Pharmaceutics and Biopharmaceutics, Universite Libre de Bruxelles, Bruxelles, Belgium
    Eur J Pharm Biopharm 80:4-13. 2012
    ..The bioavailability of the developed formulations was within the range of other DPI insulin formulations that have reached the final stages of clinical development...
  27. doi request reprint The transcription factor B-cell lymphoma (BCL)-6 modulates pancreatic {beta}-cell inflammatory responses
    Mariana Igoillo-Esteve
    Laboratory of Experimental Medicine, Erasmus Hospital, Universite Libre de Bruxelles, 1070 Brussels, Belgium
    Endocrinology 152:447-56. 2011
    ..Further understanding of these pathways may open new possibilities to improve β-cell survival in early type 1 diabetes or after transplantation...
  28. ncbi request reprint Transcriptional regulation of the endoplasmic reticulum stress gene chop in pancreatic insulin-producing cells
    Pierre Pirot
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Diabetes 56:1069-77. 2007
    ..These results suggest a differential response of beta-cells to diverse endoplasmic reticulum stress inducers, leading to a differential regulation of Chop transcription...
  29. doi request reprint Neonatal hemochromatosis and Martinez-Frias syndrome of intestinal atresia and diabetes mellitus in a consanguineous newborn
    Dana Martinovici
    Neonatal Intensive Care Unit, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium
    Eur J Med Genet 53:25-8. 2010
    ..We suggest that neonatal hemochromatosis may be part of the Martinez-Frias syndrome. Molecular analyses in this and other reported patients with the Martinez-Frias syndrome should shed light on gut development and iron metabolism...
  30. ncbi request reprint Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets?
    Nils Welsh
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
    Diabetes 54:3238-44. 2005
    ..This makes it unlikely that locally produced IL-1beta is an important mediator of glucotoxicity to human islets and argues against the IL-1beta-NF-kappaB-Fas pathway as a common mediator for beta-cell death in type 1 and type 2 diabetes...
  31. ncbi request reprint Low density lipoprotein can cause death of islet beta-cells by its cellular uptake and oxidative modification
    Miriam Cnop
    Diabetes Research Center, Brussels Free University Vrije Universiteit Brussel, Brussels 1090, Belgium
    Endocrinology 143:3449-53. 2002
    ..It is concluded that uptake of LDL by islet beta-cells and subsequent oxidative reactions can be damaging for the cells. This process can be counteracted by HDL and VLDL, and by antioxidants...
  32. ncbi request reprint Troglitazone does not protect rat pancreatic beta cells against free fatty acid-induced cytotoxicity
    Miriam Cnop
    Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B 1090 Brussels, Belgium
    Biochem Pharmacol 63:1281-5. 2002
    ..They instead indicate that the agent may sensitize pancreatic beta cells to FFA-induced damage, raising the possibility that its use facilitates the deleterious effect of increased FFA levels on the pancreatic beta cell mass...
  33. ncbi request reprint Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue
    Amir J Guri
    Laboratory of Nutritional Immunology and Molecular Nutrition, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
    J Nutr Biochem 19:216-28. 2008
    ..We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism...
  34. ncbi request reprint The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations : distinct metabolic effects of two fat compartments
    Miriam Cnop
    Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, VA Puget Sound Health Care System, and Harborview Medical Center, Seattle, Washington 98108, USA
    Diabetes 51:1005-15. 2002
    ....
  35. ncbi request reprint Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes
    Miriam Cnop
    Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108, USA
    Diabetes Care 30:677-82. 2007
    ..First-degree relatives of individuals with type 2 diabetes are at increased risk of developing hyperglycemia...
  36. ncbi request reprint Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S
    Christine C Jensen
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, 1660 S Columbian Way, Seattle, WA 98108, USA
    Diabetes 51:2170-8. 2002
    ..Both insulin resistance and impaired beta-cell function are associated with impaired glucose metabolism in all ethnic groups, with beta-cell function seeming to be more important in determining glucose disposal...
  37. ncbi request reprint The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intra-abdominal fat
    Delma J Nieves
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and Harborview Medical Center, University of Washington, Seattle, Washington 98108, USA
    Diabetes 52:172-9. 2003
    ..Thus an atherogenic lipoprotein profile appears to be the result primarily of an increase in IAF, perhaps via insulin resistance...
  38. ncbi request reprint Increased dietary fat promotes islet amyloid formation and beta-cell secretory dysfunction in a transgenic mouse model of islet amyloid
    Rebecca L Hull
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle 98108, USA
    Diabetes 52:372-9. 2003
    ....