In vivo and in vitro regulation of [3H]glyburide binding to brain sulfonylurea receptors in obesity-prone and resistant rats by glucose

Brain Res. 1997 Nov 21;776(1-2):146-53. doi: 10.1016/s0006-8993(97)00976-1.


Select brain neurons increase their firing rate when ambient glucose levels rise, possibly via a neuronal ATP-sensitive K+ (KATP) channel and its associated sulfonylurea receptor (SUR). We used receptor autoradiographic binding of 20 nM [3H]glyburide (in the presence or absence of Gpp(NH)p which blocks binding to low-affinity sites) to assess the in vivo and in vitro effects of altering glucose availability upon high- and low-affinity binding to brain SUR. Since the brain's ability to monitor and regulate glucose metabolism is critical to maintenance of energy balance, testing was done in chow-fed male Sprague-Dawley rats which had an underlying predisposition to develop either diet-induced obesity (DIO-prone) or to be diet-resistant (DR-prone) when subsequently fed a high-energy diet. Under control conditions, both in vivo and in vitro studies showed DIO-prone rats to have reduced levels of low-, but not high-affinity [3H]glyburide binding in most forebrain areas. As compared to equiosmolar infusions of mannitol, 60 min unilateral intracarotid glucose infusions at 4 mg/kg/min in awake rats reduced low-affinity [3H]glyburide binding in numerous hypothalamic and amygdalar areas of both DR- and DIO-prone rats with little effect on high-affinity binding. Only in the paraventricular nucleus of DR-prone rats was there a phenotype-specific downregulation of low-affinity binding. Brain sections from other rats were incubated with [3H]glyburide in the presence of 0, 5 or 10 mM glucose. The resultant in vitro effects of glucose were more variable and widespread than intracarotid infusions. Here, glucose often increased low-affinity [3H]glyburide binding, particularly in DR-prone rats at 5 mM. Again, there was little effect on high-affinity binding. Thus, glucose may affect the firing of glucose-responsive neurons by indirectly altering KATP channel function via its effects on low-affinity cell body SUR.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Animals
  • Brain Chemistry / drug effects*
  • Brain Chemistry / physiology
  • Carotid Arteries
  • Diuretics, Osmotic / pharmacology
  • Energy Intake
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Glyburide / metabolism*
  • Glyburide / pharmacology
  • Hypoglycemic Agents / metabolism*
  • Hypoglycemic Agents / pharmacology
  • Injections, Intra-Arterial
  • Male
  • Mannitol / pharmacology
  • Obesity / metabolism*
  • Potassium Channels / metabolism*
  • Potassium Channels / physiology
  • Potassium Channels, Inwardly Rectifying*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / metabolism*
  • Sulfonylurea Receptors
  • Tritium


  • ATP-Binding Cassette Transporters
  • Diuretics, Osmotic
  • Hypoglycemic Agents
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Tritium
  • Mannitol
  • Glucose
  • Glyburide