The influence of insulin on circulating ghrelin

Daniel E. Flanagan, Mark L. Evans, Teresa P. Monsod, Frances Rife, Rubina A. Heptulla, William V. Tamborlane, Robert S. Sherwin

Research output: Contribution to journalArticlepeer-review

326 Scopus citations


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 μg/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.

Original languageEnglish (US)
Pages (from-to)E313-E316
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 47-2
StatePublished - Feb 1 2003


  • Glucose clamp
  • Growth hormone
  • Hypoglycemia
  • Hypothalamus
  • Somatostatin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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