Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters

Citation
Sq. Luo et al., Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters, NEUROENDOCR, 69(3), 1999, pp. 160-166
Citations number
56
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROENDOCRINOLOGY
ISSN journal
00283835 → ACNP
Volume
69
Issue
3
Year of publication
1999
Pages
160 - 166
Database
ISI
SICI code
0028-3835(199903)69:3<160:IAOBAT>2.0.ZU;2-H
Abstract
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.