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Background The octanoylated peptide ghrelin stimulates growth hormone (GH) secretion during severe calorie restriction in mice, which preserves fasting blood sugar after body fat has been depleted. Genetic deletion of ghrelin-O-acyltransferase (GOAT, which octanoylates ghrelin) renders mice ghrelin-deficient and abrogates the normal rise in GH after several days of calorie restriction, resulting in profound hypoglycemia. Administration of either ghrelin or GH to GOAT knockout mice restores the ability to maintain fasting blood sugar levels during prolonged calorie restriction. The mechanism of hypoglycemia in ghrelin-deficient mice has not been described previously.

The ghrelin-growth hormone axis preserves gluconeogenesis to maintain blood glucose levels during starvation