Endocrine Abstracts (2002) 3 P180

Ghrelin is acutely regulated by insulin but not glucose

DEH Flanagan, ML Evans, TP Monsod, F Rife, RA Heptulla, WV Tamborlane & RS Sherwin

Section of Endocrinology, Yale University School of Medicine, New Haven, USA.

Ghrelin is a novel peptide that acts on the growth hormone segratagogue receptor in the pituitary and hypothalamus. It functions as a third physiological regulator of GH secretion along with GHRH 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. Whilst 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, using a stepped hyperinsulinemic eu- hypo- hyperglycemic glucose clamp, that either hyperinsulinemia or hypoglycemia may influence ghrelin production. Having been stable in the period prior to the clamp ghrelin rapidly fell at the onset of the insulin infusion during euglycemia (baseline ghrelin 207 se 12 fmol/ml vs 169 se 10 fmol\/ml at t =30 minutes p< 0.001). Ghrelin remained suppressed during subsequent periods of hypoglycemia (mean glucose 53 se 2 mg/dl) and hyperglycemia (mean glucose 163 se 6 mg/dl). Despite suppression of ghrelin, growth hormone showed a significant rise during hypoglycemia (baseline 4.1 se 1.3 mcg/l vs 28.2 se 3.9 mcg/l at t= 120 minutes p < 0.001).

In conclusion our data suggests that insulin plays a role in the postprandial suppression of ghrelin but that blood glucose level has little additional effect. The rise in growth hormone seen in response to hypoglycemia is not regulated by ghrelin.

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