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Pancreatic β-cell α2A adrenoceptor and phospholipid changes in hyperlipidemic ratsadrenoceptor and phospholipid changes in hyperlipidemic rats

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Lipids

Abstract

We previously showed that a 48-h intravenous lipid infusion in rats induces pancreatic β-cell hypersensitivity to catecholamines. Our aim was to study the lipid-related changes that may account for such hypersensitivity in pancreatic islets. We show here that a 48-h increase in plasma FFA alters the binding characteristics of β-cell α2 adrenoceptors in rats. Lipid infusion decreases pancreatic norepinephrine (NE) turnover rate by 28%, reflecting a reduction of pancreatic NE stores. Following lipid infusion, the density of α2 adrenoceptor binding sites is significantly lower and receptor affinity higher, both in islet homogenates (by three- and fivefold, respectively) and isolated whole β-cells (by two- and sixfold, respectively). These changes correlate with the elevated insulin response to glucose found in lipid-infused rats. We also found a modification of islet phospholipid content, particularly in phosphoethanolamine species containing infused FA such as palmitate, oleate, stearate, and linoleate. This may account for the modifications in receptor affinity. These results suggest that hyperlipidemia-associated pathologies such as diabetes and obesity not only may result from alterations of metabolic pathways but also may be a consequence of early modifications in nervous firing rates and signal transduction pathways.

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Abbreviations

ESL:

electrospray ionization

FACS:

fluorescence-activated cell sorting

FAD:

flavin adenine dinucleotide

GIIS:

glucose-induced insulin secretion

IL:

Intralipid

KRBH buffer:

Krebs-Ringer-bicarbonate-Hepes

NE:

norepinephrine

POPE:

palmitoyl-oleoyl-PE

RT-PCR:

reverse transcription-PCR

[3H]RX821002:

2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline, a benzodioxane derivative that exhibits high affinity for α2-adrenergic receptors

TM buffer:

Tris-HCl/MgCl2 buffer

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Authors and Affiliations

  1. Laboratoire de Physiopathologie de la Nutrition CNRS UMR 7059, Université Paris 7, 75251, Paris cedex 05

    L. Clément, K. -A. Kim-Sohn, C. Magnan, N. Kassis & A. Ktorza

  2. Merck-Lipha, Chilly Mazarin, France

    P. Adnot & M. Kergoat

  3. Departement de Biochimie Médicale, Centre Médical Universitaire, CH1211, Genèva 4, Switzerland

    F. Assimacopoulos-Jeannet

  4. Laboratoire de Neurobiologie, Plasticité Tissulaire et Métabolisme Energétique, CNRS UMR 5018, Université Paul Sabatier, CHU Rangueil, 31000, Toulouse, France

    L. Pénicaud

  5. Mass Spectrometry Resource, Department of Medicine, Washington University School of Medicine, 63110, St. Louis, Missouri

    F. -F. Hsu & J. Turk

Authors
  1. L. Clément
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  2. K. -A. Kim-Sohn
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  3. C. Magnan
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  4. N. Kassis
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  9. F. -F. Hsu
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  10. J. Turk
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  11. A. Ktorza
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Correspondence to L. Clément.

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Clément, L., Kim-Sohn, K.A., Magnan, C. et al. Pancreatic β-cell α2A adrenoceptor and phospholipid changes in hyperlipidemic ratsadrenoceptor and phospholipid changes in hyperlipidemic rats. Lipids 37, 501–506 (2002). https://doi.org/10.1007/s11745-002-0924-0

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  • DOI: https://doi.org/10.1007/s11745-002-0924-0

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