Liver Autophagy Contributes to the Maintenance of Blood Glucose and Amino Acid Levels

Autophagy. 2011 Jul;7(7):727-36. doi: 10.4161/auto.7.7.15371. Epub 2011 Jul 1.

Abstract

Both anabolism and catabolism of the amino acids released by starvation-induced autophagy are essential for cell survival, but their actual metabolic contributions in adult animals are poorly understood. Herein, we report that, in mice, liver autophagy makes a significant contribution to the maintenance of blood glucose by converting amino acids to glucose via gluconeogenesis. Under a synchronous fasting-initiation regimen, autophagy was induced concomitantly with a fall in plasma insulin in the presence of stable glucagon levels, resulting in a robust amino acid release. In liver-specific autophagy (Atg7)-deficient mice, no amino acid release occurred and blood glucose levels continued to decrease in contrast to those of wild-type mice. Administration of serine (30 mg/animal) exerted a comparable effect, raising the blood glucose levels in both control wild-type and mutant mice under starvation. Thus, the absence of the amino acids that were released by autophagic proteolysis is a major reason for a decrease in blood glucose. Autophagic amino acid release in control wild-type livers was significantly suppressed by the prior administration of glucose, which elicited a prompt increase in plasma insulin levels. This indicates that insulin plays a dominant role over glucagon in controlling liver autophagy. These results are the first to show that liver-specific autophagy plays a role in blood glucose regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood*
  • Animals
  • Autophagy*
  • Blood Glucose / metabolism*
  • Fasting / blood
  • Fatty Acids / blood
  • Glucagon / blood
  • Gluconeogenesis
  • Insulin / blood
  • Liver / cytology*
  • Liver / metabolism*
  • Liver / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Starvation
  • Triglycerides / blood
  • Vacuoles / metabolism
  • Vacuoles / ultrastructure

Substances

  • Amino Acids
  • Blood Glucose
  • Fatty Acids
  • Insulin
  • MAP1LC3 protein, mouse
  • Microtubule-Associated Proteins
  • Triglycerides
  • Glucagon