Characterization of Glucosensing Neuron Subpopulations in the Arcuate Nucleus

Integration in Neuropeptide Y and Pro-Opio Melanocortin Networks?

  1. Xavier Fioramonti1,
  2. Sylvain Contié1,
  3. Zhentao Song2,
  4. Vanessa H. Routh2,
  5. Anne Lorsignol1 and
  6. Luc Pénicaud1
  1. 1Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5018, Paul Sabatier University, Toulouse, France
  2. 2Department of Pharmacology and Physiology, New Jersey Medical School, Newark, New Jersey
  1. Address correspondence and reprint requests to Dr. Anne Lorsignol, UMR 5018 CNRS-Université Paul Sabatier, IFR31, BP84225, 31403 Toulouse Cedex 4, France. E-mail: anne.lorsignol{at}toulouse.inserm.fr

Abstract

Four types of responses to glucose changes have been described in the arcuate nucleus (ARC): excitation or inhibition by low glucose concentrations <5 mmol/l (glucose-excited and -inhibited neurons) and by high glucose concentrations >5 mmol/l (high glucose–excited and –inhibited neurons). However, the ability of the same ARC neuron to detect low and high glucose concentrations has never been investigated. Moreover, the mechanism involved in mediating glucose sensitivity in glucose-inhibited neurons and the neurotransmitter identity (neuropeptide Y [NPY] or pro-opio melanocortin [POMC]) of glucosensing neurons has remained controversial. Using patch-clamp recordings on acute mouse brain slices, successive extracellular glucose changes greater than and less than 5 mmol/l show that glucose-excited, high glucose–excited, glucose-inhibited, and high glucose–inhibited neurons are different glucosensing cell subpopulations. Glucose-inhibited neurons directly detect decreased glucose via closure of a chloride channel. Using transgenic NPY–green fluorescent protein (GFP) and POMC-GFP mice, we show that 40% of NPY neurons are glucose-inhibited neurons. In contrast, <5% of POMC neurons responded to changes in extracellular glucose >5 mmol/l. In vivo results confirm the lack of glucose sensitivity of POMC neurons. Taken together, hypo- and hyperglycemia are detected by distinct populations of glucosensing neurons, and POMC and NPY neurons are not solely responsible for ARC glucosensing.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 29 January 2007. DOI: 10.2337/db06-0567.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted January 22, 2007.
    • Received April 27, 2006.
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  1. Diabetes vol. 56 no. 5 1219-1227
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