title: The influence of insulin on circulating ghrelin.
abstract: Ghrelin is a novel peptide that acts on the growth hormone (GH) secretagogue receptor in the pituitary and hypothalamus. It may function as a third physiological regulator of GH secretion, along with GH-releasing hormone and somatostatin. In addition to the action of ghrelin on the GH axis, it appears to have a role in the determination of energy homeostasis. Although feeding suppresses ghrelin production and fasting stimulates ghrelin release, the underlying mechanisms controlling this process remain unclear. The purpose of this study was to test the hypotheses, by use of a stepped hyperinsulinemic eu- hypo- hyperglycemic glucose clamp, that either hyperinsulinemia or hypoglycemia may influence ghrelin production. Having been stable in the period before the clamp, ghrelin levels rapidly fell in response to insulin infusion during euglycemia (baseline ghrelin 207 +/- 12 vs. 169 +/- 10 fmol/ml at t = 30 min, P < 0.001). Ghrelin remained suppressed during subsequent periods of hypoglycemia (mean glucose 53 +/- 2 mg/dl) and hyperglycemia (mean glucose 163 +/- 6 mg/dl). Despite suppression of ghrelin, GH showed a significant rise during hypoglycemia (baseline 4.1 +/- 1.3 vs. 28.2 +/- 3.9 microg/l at t = 120 min, P < 0.001). Our data suggest that insulin may suppress circulating ghrelin independently of glucose, although glucose may have an additional effect. We conclude that the GH response seen during hypoglycemia is not regulated by circulating ghrelin.
authors.affiliation: Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Flanagan
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.forename: Teresa P
authors.initials: TP
authors.lastname: Monsod
authors.forename: Frances
authors.initials: F
authors.lastname: Rife
authors.forename: Rubina A
authors.initials: RA
authors.lastname: Heptulla
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D054439:Ghrelin; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D036361:Peptide Hormones / Q000097:blood*
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007004:Hypoglycemic Agents; D007328:Insulin; D036361:Peptide Hormones