Growth hormone acts on liver to stimulate autophagy, support glucose production, and preserve blood glucose in chronically starved mice

Significance Nine million people starve to death annually. To understand starvation, we created a mouse model in which the mice receive a daily meal that contains 40% of normal calories. They consume each meal within 1 hour and fast for 23 hours. Normal mice maintain viable levels of blood glucose by increasing hepatic glucose production. Gluconeogenesis requires elevated plasma growth hormone (GH) and is accompanied by hepatic autophagy. GH-deficient mice become hypoglycemic, owing to decreased autophagy and glucose production. Here we show that mice lacking the liver GH receptor have reduced autophagy and become hypoglycemic. These data demonstrate that GH acts through its receptor in the liver to induce autophagy and enhance glucose production, maintaining blood glucose during famine.