Sq. Luo et al., Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters, NEUROENDOCR, 69(3), 1999, pp. 160-166
Bromocriptine, a potent dopamine D-2 receptor agonist, suppresses lipogenes
is and improves glucose intolerance and insulin resistance. Recent evidence
suggests that bromocriptine may produce these effects by altering central
nervous system (CNS) regulation of metabolism. To determine whether or not
the CNS plays a critical role in these bromocriptine-mediated effects on pe
ripheral metabolism, we compared the metabolic responses to bromocriptine w
hen administered peripherally versus centrally in naturally obese and gluco
se intolerant Syrian hamsters. Male hamsters (BW 194 +/- 5 g) were treated
with bromocriptine or vehicle either intraperitoneally (i.p., 800 mu g/anim
al) or intracerebroventricularly (i.c.v., 1 mu g/animal) daily at Ih after
light onset for 14 days while held on 14-hour daily photoperiods. Glucose t
olerance tests (GTTs, 3 g glucose/kg BW) were conducted after treatment. Co
mpared to control animals, bromocriptine i.p, significantly reduced weight
gain (11.7 vs. -2.4 g) and the areas under the glucose and insulin GTT curv
es by 29 and 48%, respectively. Similarly, compared with vehicle-treated co
ntrols, bromocriptine i.c.v. at 1 mu g/animal substantially reduced weight
gain (8.7 vs. -6.3 g), the areas under the glucose and insulin GTT curves b
y 31 and 44% respectively, and the basal plasma insulin concentration by 41
% (p < 0.05). Furthermore, both treatments significantly improved insulin-m
ediated suppression of hepatic glucose production during a hyperinsulinemic
-euglycemic clamp. Thus, daily administration of bromocriptine at a very lo
w dose i.c.v. replicates the metabolic effects of bromocriptine administere
d i.p. at a much higher dose. This finding demonstrates for the first time
that the CNS is a critical target of bromocriptine's metabolic effects.