Circulating ghrelin concentrations are lowered by intracerebroventricular insulin

Aims/hypothesis 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 whet...

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Bibliographic Details
Published in:Diabetologia 2006-10, Vol.49 (10), p.2449-2452
Main Authors: Ueno, M, Carvalheira, J. B. C, Oliveira, R. L. G. S, Velloso, L. A, Saad, M. J. A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
CNS
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Food
Food Deprivation
Ghrelin
Glucose
Growth factors
Hypothalamus
Hypothalamus - drug effects
Hypothalamus - physiology
Injections, Intraventricular
Insulin
Insulin - administration & dosage
Insulin - pharmacology
Kinases
Kinetics
Medical sciences
Mitogen-Activated Protein Kinases - metabolism
Nervous system
Peptide Hormones - blood
Peptide Hormones - drug effects
Peptides
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Plasma
Proteins
Rats
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Summary:Aims/hypothesis 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/interpretation 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.
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-006-0371-8