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

Brain Research
B E Levin, Ambrose A Dunn-Meynell

Abstract

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 o...Continue Reading

Citations

Mar 24, 1998·Annual Review of Medicine·E M BrownS C Hebert
Feb 22, 2007·American Journal of Physiology. Endocrinology and Metabolism·Maricedes Acosta-Martínez, Jon E Levine
Oct 12, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Nancy C Tkacs, Barry E Levin
May 8, 1999·The American Journal of Physiology·B E LevinV H Routh
Sep 23, 1998·Brain Research Bulletin·B E Levin, A A Dunn-Meynell
May 4, 2001·European Journal of Pharmacology·L G GonzálezJ M Baeyens

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