Circulating ghrelin concentrations are lowered by intracerebroventricular insulin.
OBJECTIVE
Ghrelin is a peptide that is mainly produced by the stomach and stimulates food intake, adiposity and weight gain. Previous studies have documented that plasma levels of ghrelin are reduced by insulin, but the mechanisms that mediate this effect are unclear.


METHODS
To determine whether phosphatidylinositol 3-kinase (PI(3)K) and/or mitogen-activated protein kinase (MAPK) are involved in this insulin action, we tested the intracerebroventricular (i.c.v.) effect of specific inhibitors of PI(3)K (LY294002 and wortmannin) and MAPK (PD98059 and UO126) on the insulin-mediated reduction of ghrelin levels in rats.


RESULTS
Intracerebroventricular treatment with insulin reduced ghrelin levels. Inhibition of PI(3)K specifically blocked the insulin-induced reduction in ghrelin concentration, whereas inhibition of MAPK had no effect on insulin-mediated actions. Moreover, pretreatment with i.c.v. PI(3)K inhibitors blocked the reduction of ghrelin levels after OGTT-induced hyperglycaemia and hyperinsulinaemia.


CONCLUSIONS
These data demonstrate that changes in insulin action in the central nervous system regulate circulating ghrelin levels and that PI(3)K is a specific mediator of this action.
Ueno
M
M
Department of Internal Medicine, State, University of Campinas (UNICAMP), Campinas, São Paulo, 13081-970, Brazil.
Carvalheira
J B C
JB
Oliveira
R L G S
RL
Velloso
L A
LA
Saad
M J A
MJ
D000818:Animals; D005508:Food Deprivation; D054439:Ghrelin; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D036361:Peptide Hormones / Q000097:blood* / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats
D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases