Be. Levin et al., DIFFERENTIAL-EFFECTS OF DIET AND OBESITY ON HIGH AND LOW-AFFINITY SULFONYLUREA BINDING-SITES IN THE RAT-BRAIN, Brain research, 739(1-2), 1996, pp. 293-300
yThe brain contains neurons which alter their firing rates when ambien
t glucose concentrations change. An ATP-sensitive K+ (K-atp) channel o
n these neurons closes and increases cell firing when ATP is produced
by intracellular glucose metabolism. Binding of the antidiabetic sulfo
nylurea drugs to a site linked to this channel has a similar effect. H
ere rats with a propensity to develop diet-induced obesity (DIG) or to
be diet-resistant (DR) when fed a diet moderately high in fat, energy
and sucrose (HE diet) had low and high affinity sulfonylurea binding
assessed autoradiographically with [H-3]glyburide in the presence or a
bsence of Gpp(NH)p. Before HE diet exposure, chow-fed DIO- and DR-pron
e rats were separated by their high vs. low 24 h urine NE levels. In D
R-prone rats, low affinity [H-3]glyburide binding sites comprised up t
o 45% of total binding with highest concentrations in the hypothalamus
and amygdala. But DIG-prone rats had few or no low affinity binding s
ites throughout the forebrain. High affinity [H-3]glyburide binding wa
s similar between phenotypes. When rats developed DIO after 3 months o
n HE diet, their low affinity binding increased slightly. DR rats fed
the HE diet gained the same amount of weight as chow-fed controls but
their low affinity binding sites were reduced to DIG levels and both w
ere significantly lower than chow-fed controls. By contrast, high affi
nity [H-3]glyburide binding was increased in DR rats throughout the fo
rebrain so that it significantly exceeded that in both DIO and chow-fe
d control rats. These studies demonstrate a significant population of
low affinity sulfonylurea binding sites throughout the forebrain which
, along with high affinity sites, are regulated as a function of both
weight gain phenotype and diet composition.