Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons

Am J Physiol Regul Integr Comp Physiol. 2014 Feb 15;306(4):R257-64. doi: 10.1152/ajpregu.00451.2013. Epub 2013 Dec 31.


Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component.

Keywords: 5-thio-d-glucose; catecholamine neurons; feeding; glucosamine; phloridzin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Catecholamines / metabolism*
  • Eating / drug effects
  • Eating / physiology*
  • Glucosamine / pharmacology
  • Glucose / analogs & derivatives
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phlorhizin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rhombencephalon / drug effects
  • Rhombencephalon / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Catecholamines
  • 5-thio-D-glucose
  • Phlorhizin
  • Glucose
  • Glucosamine