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Team Emmanuel VAN OBBERGHEN

Presentation

Basic Research Team  « Aging and Diabetes »


Pr Emmanuel VAN OBBERGHEN, PU-PH Emeritus, Team Leader



Research Project

Diabetes and cardiovascular diseases afflict an increasing percentage of the ageing population. A tight link exists between these pathologies as diabetes predisposes to cardiac failure and conversely cardiovascular complications are the chief cause of increased mortality in diabetes. Both environmental/lifestyle factors and genetic factors participate in the defects of type 2 diabetes (T2D), which are insufficient insulin secretion and insulin resistance. An emerging paradigm is that the risk of chronic diseases in adult life is accounted for, at least in part, environmental influences, particularly those occurring in utero. Supporting this is the increased T2D risk in offspring of overfed mothers or exposed to deleterious uterine conditions. Our hypothesis is that under deleterious in utero conditions, the altered control exerted by miRNAs on gene regulation increases the risk of insulin resistance and T2D in adult life. We study offsprings of rat dams exposed during pregnancy to an inappropriate diet or to a deficient uterine environment, leading to increased insulin resistance and T2D risk, and identify miRNAs with modified expression in the liver and pancreas of the offspring. We also study the impact of the deleterious maternal environment on cardiac development.

The age-related increase in T2D involves beta cell failure due to insulin resistance. Therefore, we investigate whether age-related alterations in the dialogue between beta cells and endothelial cells participate in pancreatic insufficiency. Finally, as both ageing and diabetes have deleterious effects on kidney function we investigate the potential role of insulin resistance related factors on the kidney.

We believe that our multipronged approach using powerful cutting edge technologies will allow us to develop our proposal successfully, and significantly advance the understanding of the mechanisms leading to increased diabetes incidence during ageing. Our project will have important medical implications by fostering the development of prevention strategies for T2D and its cardiovascular complications, and may in the future harness the epidemic growth of the diseases. Hence the impact of our endeavour is likely to lead to health promotion.


Research Team

Research Team


VAN OBBERGHEN Emmanuel, PU-PH CE Emeritus, Team Leader
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CANIVET Bertrand, PU-PH1
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CHINETTI Giulia, PU-PH1

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DUMORTIER Olivier, Post-doc
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ESNAULT Vincent, PU-PH1
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FABRIS Gaia, PhD Student

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FAVRE Guillaume, PH (Contrat interface INSERM)
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GAUTIER Nadine, IEHC INSERM (80 %)
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HINAULT Charlotte, MCU-PH
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ICHAI Carole, PU-PH1
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LAREYRE Fabien, PhD Student

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LEBRUN Patricia, MCU UNS
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MANFRONI Georges, TCN INSERM (50 %)
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NAIMI Mourad, MCU-PH1
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ORBAN Jean-Christophe, PH
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PANAIA-FERRARI Patricia, PH

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RAFFORT Juliette, PhD Student

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ROGER Estelle, PhD Student

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SENLIS Jean-Eric, AHU
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Awards

May 2016 :

Pr Emmanuel Van Obberghen received the Paul Langerhans award.

This is the most important award granted by the German Diabetes Society. 

 




    Publications

    Publications


    2015


    Raffort J, Hinault C, Dumortier O, Van Obberghen E.

    Circulating microRNAs and diabetes: potential applications in medical practice.

    Diabetologia, 2015, Sep;58(9):1978-92.


    Favre GA, Esnault VL, Van Obberghen E.

    Modulation of glucose metabolism by the renin-angiotensin-aldosterone system.

    Am J Physiol Endocrinol Metab., 2015, Mar 15;308(6):E435-49.


    2014


    Favre GA, Lebrun P, Lopez P, Butori C, Hofman P, Esnault VL, Van Obberghen E.

    Constitutive activation of the renin-angiotensin system reduces visceral fat and improves

    glucose tolerance in mice.

    J Renin Angiotensin Aldosterone Syst., 2014, Dec;15(4):396-409.


    Orban JC, Maizière EM, Ghaddab A, Van Obberghen E, Ichai C.

    Incidence and characteristics of acute kidney injury in severe diabetic ketoacidosis.

    PLoS One, 2014, Oct 22;9(10):e110925.


    Dumortier O, Hinault C, Gautier N, Patouraux S, Casamento V, Van Obberghen E.

    Maternal protein restriction leads to pancreatic failure in offspring: role of misexpressed

    microRNA-375.

    Diabetes. 2014 Oct;63(10):3416-27.


    Favre GA, Touzot M, Fremeaux-Bacchi V, Hyvernat H, Gueffet JP, Rohrlich PS, Queyrel V,

    Esnault V, Fakhouri F.

    Malignancy and thrombotic microangiopathy or atypical haemolytic and uraemic syndrome ?

    British J Hematol, 2014, John Wiley & Sons Ltd., doi :10.1111/bjh-12907.


    Bonesso L, Piraud M, Caruba C, Van Obberghen E, Mengual R, Hinault C.
    Fast urinary screening of oligosaccharidoses by MALDI-TOF/TOF mass
    spectrometry.
    Orphanet J Rare Dis., 2014, Feb 6;9(1):19.

    2013

    Hinault C, Dumortier O, Van Obberghen E.,
    MicroRNA and diabetes : tiny things causing huge effects.
    Med Sci (Paris). 2013, 29(8-9):785-90.

    Dumortier O, Hinault C, Van Obberghen E.,
    MicroRNAs and Metabolism Crosstalk in Energy Homeostasis.
    Cell Metab. 2013 Sep 3;18(3):312-24.

    2012

    Dumortier O, Van Obberghen E
    MicroRNAs in pancreas development.
    Diabetes Obes Metab., 2012, 14 Suppl 3:22-28.

    2011

    Fiory F, Lombardi A, Miele C, Giudicelli J, Beguinot F, Van Obberghen E
    Methylglyoxal impairs insulin signalling and insulin action on glucose-induced insulin secretion
    in the pancreatic beta cell line INS-1E.
    Diabetologia, 2011, 54:2941-2952.

    Arous C, Naimi M, Van Obberghen E
    Oleate-mediated activation of phospholipase D and mammalian target of rapamycin (mTOR)
    regulates proliferation and rapamycin sensitivity of hepatocarcinoma cells.
    Diabetologia, 2011, 54:954-964.

    2010

    Naimi M, Arous C, Van Obberghen E
    Energetic cell sensors: a key to metabolic homeostasis.
    Trends Endocrinol Metab., 2010, 21:75-82.

    Lebrun P, Cognard E, Gontard P, Bellon-Paul R, Filloux C, Berthault MF, Magnan C,
    Ruberte J, Luppo M, Pujol A, Pachera N, Herchuelz A, Bosch F, Van Obberghen E
    The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion.
    Diabetologia, 2010, 53:1935-1946.

    2009

    Lebrun P, Cognard E, Bellon-Paul R, Gontard P, Filloux C, Jehl-Pietri C, Grimaldi P,
    Samson M, Penicaud L, Ruberte J, Ferre T, Pujol A, Bosch F, Van Obberghen E
    Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle
    leads to reduced mobility and overweight in mice.
    Diabetologia, 2009, 52:2201-2212.

    Hasseine LK, Hinault C, Lebrun P, Gautier N, Paul-Bellon R, Van Obberghen E
    miR-139 impacts FoxO1 action by decreasing FoxO1 protein in mouse hepatocytes.
    Biochem Biophys Res Commun., 2009, 390:1278-1282.

    Baroukh NN, Van Obberghen E
    Function of microRNA-375 and microRNA-124a in pancreas and brain.
    Febs J., 2009, 276:6509-6521.

    2008

    Segalen C, Longnus SL, Baetz D, Counillon L, Van Obberghen E
    5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside reduces glucose uptake
    via the inhibition of Na+/H+ exchanger 1 in isolated rat ventricular cardiomyocytes.
    Endocrinology, 2008, 149:1490-1498.

    El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D, van Obberghen E
    miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates
    glucose-induced biological responses in pancreatic beta-cells.
    Diabetes, 2008, 57:2708-2717.

    Demozay D, Mas JC, Rocchi S, Van Obberghen E
    FALDH reverses the deleterious action of oxidative stress induced by lipid peroxidation
    product 4-hydroxynonenal on insulin signaling in 3T3-L1 adipocytes.
    Diabetes, 2008, 57:1216-1226.

    2007

    Naimi M, Gautier N, Chaussade C, Valverde AM, Accili D, Van Obberghen E
    Nuclear forkhead box O1 controls and integrates key signaling pathways in hepatocytes.
    Endocrinology, 2007, 148:2424-2434.

    Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, Rutter GA,
    Van Obberghen E
    MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic
    beta-cell lines.
    J Biol Chem., 2007, 282:19575-19588.

    2006

    Riboulet-Chavey A, Pierron A, Durand I, Murdaca J, Giudicelli J, Van Obberghen E
    Methylglyoxal impairs the insulin signaling pathways independently of the formation
    of intracellular reactive oxygen species.
    Diabetes, 2006, 55:1289-1299.

    Hinault C, Mothe-Satney I, Gautier N, Van Obberghen E
    Amino acids require glucose to enhance, through phosphoinositide-dependent
    protein kinase 1, the insulin-activated protein kinase B cascade in insulin-resistant
    rat adipocytes.
    Diabetologia, 2006, 49:1017-1026.


    (Feb 2016)


    Financial Grants

    Financial Grants